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Ritobrata Goswami - One of the best experts on this subject based on the ideXlab platform.
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calcitriol attenuates tlr2 il 33 signaling pathway to repress Th9 Cell differentiation and potentially limits the pathophysiology of rheumatoid arthritis
Molecular and Cellular Biochemistry, 2021Co-Authors: Shachi Pranjal Vyas, Rajeshwar Nath Srivastava, Ritobrata GoswamiAbstract:There is limited information regarding the TLR2 signaling pathway involved in Th9 Cell differentiation. The role of calcitriol in regulating TLR2-mediated Th9 Cell development is unknown. Thus, we aimed to unravel the TLR2 signaling pathway in Th9 Cells and its regulation by calcitriol. We have used n = 5-6 animals for each murine experiment. Human studies involved five healthy volunteers. Moreover, ten healthy individuals and ten RA patients were included in the study. Murine and human Th9 Cells were treated with Calcitriol (100 nM) and Pam3CSK4 (2 µg/mL). The number of IL-9+ve Cells was determined by flow cytometry. Real-time PCR was used to assess the gene expression. Serum 25(OH)D3 levels were determined by HPLC. We observed that TLR2 signals via IL-33/ST2 in Th9 Cells. Increased TLR2 expression associated with increased IL9 expression and augmented disease severity in RA patients. Calcitriol attenuated TLR2 signaling in murine and human Th9 Cells. Low serum vitamin D3 level negatively associated with increased IL-9 and TLR2 expression and disease severity in RA patients. Our data suggest a potential role of calcitriol to ameliorate the disease severity of RA patients.
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Calcitriol attenuates TLR2/IL-33 signaling pathway to repress Th9 Cell differentiation and potentially limits the pathophysiology of rheumatoid arthritis
Molecular and Cellular Biochemistry, 2020Co-Authors: Shachi Pranjal Vyas, Rajeshwar Nath Srivastava, Ritobrata GoswamiAbstract:There is limited information regarding the TLR2 signaling pathway involved in Th9 Cell differentiation. The role of calcitriol in regulating TLR2-mediated Th9 Cell development is unknown. Thus, we aimed to unravel the TLR2 signaling pathway in Th9 Cells and its regulation by calcitriol. We have used n = 5–6 animals for each murine experiment. Human studies involved five healthy volunteers. Moreover, ten healthy individuals and ten RA patients were included in the study. Murine and human Th9 Cells were treated with Calcitriol (100 nM) and Pam_3CSK_4 (2 µg/mL). The number of IL-9+ve Cells was determined by flow cytometry. Real-time PCR was used to assess the gene expression. Serum 25(OH)D_3 levels were determined by HPLC. We observed that TLR2 signals via IL-33/ST2 in Th9 Cells. Increased TLR2 expression associated with increased IL9 expression and augmented disease severity in RA patients. Calcitriol attenuated TLR2 signaling in murine and human Th9 Cells. Low serum vitamin D3 level negatively associated with increased IL-9 and TLR2 expression and disease severity in RA patients. Our data suggest a potential role of calcitriol to ameliorate the disease severity of RA patients.
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Calcitriol Regulates the Differentiation of IL-9-Secreting Th9 Cells by Modulating the Transcription Factor PU.1.
Journal of immunology (Baltimore Md. : 1950), 2020Co-Authors: Shachi Pranjal Vyas, Mark H Kaplan, Arman Kunwar Hansda, Ritobrata GoswamiAbstract:Vitamin D can modulate the innate and adaptive immune system. Vitamin D deficiency has been associated with various autoimmune diseases. Th9 Cells are implicated in the pathogenesis of numerous autoimmune diseases. Thus, we investigated the role of calcitriol (active metabolite of vitamin D) in the regulation of Th9 Cell differentiation. In this study, we have unraveled the molecular mechanisms of calcitriol-mediated regulation of Th9 Cell differentiation. Calcitriol significantly diminished IL-9 secretion from murine Th9 Cells associated with downregulated expression of the Th9-associated transcription factor, PU.1. Ectopic expression of VDR in Th9 Cells attenuated the percentage of IL-9-secreting Cells. VDR associated with PU.1 in Th9 Cells. Using a series of mutations, we were able to dissect the VDR domain involved in the regulation of the Il9 gene. The VDR-PU.1 interaction prevented the accessibility of PU.1 to the Il9 gene promoter, thereby restricting its expression. However, the expression of Foxp3, regulatory T Cell-specific transcription factor, was enhanced in the presence of calcitriol in Th9 Cells. When Th9 Cells are treated with both calcitriol and trichostatin A (histone deacetylase inhibitor), the level of IL-9 reached to the level of wild-type untreated Th9 Cells. Calcitriol attenuated specific histone acetylation at the Il9 gene. In contrast, calcitriol enhanced the recruitment of the histone modifier HDAC1 at the Il9 gene promoter. In summary, we have identified that calcitriol blocked the access of PU.1 to the Il9 gene by reducing its expression and associating with it as well as regulated the chromatin of the Il9 gene to regulate expression.
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A Decade of Th9 Cells: Role of Th9 Cells in Inflammatory Bowel Disease.
Frontiers in immunology, 2018Co-Authors: Shachi Pranjal Vyas, Ritobrata GoswamiAbstract:T helper Cell subsets play a critical role in providing protection against offending pathogens by secreting specific cytokines. However, unrestrained T helper Cell responses can promote chronic inflammation-mediated inflammatory diseases. Dysregulated T helper Cell responses have been suggested to be involved in the pathogenesis of multiple inflammatory diseases, including allergic airway inflammation, rheumatoid arthritis, and inflammatory bowel disease (IBD) among others. Aberrant pro-inflammatory responses induced by Th1, Th2, and Th17 subsets are known to trigger IBD. IBD is a chronic inflammatory disease characterized by weight loss, diarrhea, pain, fever, and rectal bleeding. It poses a major health burden worldwide owing to the increased risk of colorectal cancer development. Despite numerous therapeutic advancements, IBD still remains a major health burden due to the inefficiency of the conventional therapies. Recently, IL-9-secreting Th9 Cells are known to be involved in the pathogenesis of IBD. However, the role of Th9 Cells and their secretory cytokine IL-9 in IBD is unclear. The functional relevance of Th9 Cells is also relatively understudied in IBD. Thus, investigating the actual role of various T helper Cell subsets including Th9 Cells in IBD is essential to develop novel therapies to treat IBD. Here, we highlight the role of Th9 Cells in promoting IBD. We discuss the mechanisms that might be employed by Th9 Cells and IL-9 in promoting IBD and thereby propose potential targets for the treatment of Th9 Cell-mediated IBD.
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Th9 Cell development requires a BATF-regulated transcriptional network
The Journal of clinical investigation, 2013Co-Authors: Rukhsana Jabeen, Ritobrata Goswami, Evelyn T Nguyen, Olufolakemi Awe, Aishwarya Kulkarni, Andrea Attenasio, Daniel Walsh, Matthew R. Olson, Myung H. Kim, Robert S TepperAbstract:T helper 9 (Th9) Cells are specialized for the production of IL-9, promote allergic inflammation in mice, and are associated with allergic disease in humans. It has not been determined whether Th9 Cells express a characteristic transcriptional signature. In this study, we performed microarray analysis to identify genes enriched in Th9 Cells compared with other Th subsets. This analysis defined a transcriptional regulatory network required for the expression of a subset of Th9-enriched genes. The activator protein 1 (AP1) family transcription factor BATF (B Cell, activating transcription factor–like) was among the genes enriched in Th9 Cells and was required for the expression of IL-9 and other Th9-associated genes in both human and mouse T Cells. The expression of BATF was increased in Th9 cultures derived from atopic infants compared with Th9 cultures from control infants. T Cells deficient in BATF expression had a diminished capacity to promote allergic inflammation compared with wild-type controls. Moreover, mouse Th9 Cells ectopically expressing BATF were more efficient at promoting allergic inflammation than control transduced Cells. These data indicate that BATF is a central regulator of the Th9 phenotype and contributes to the development of allergic inflammation.
Mark H Kaplan - One of the best experts on this subject based on the ideXlab platform.
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Calcitriol Regulates the Differentiation of IL-9-Secreting Th9 Cells by Modulating the Transcription Factor PU.1.
Journal of immunology (Baltimore Md. : 1950), 2020Co-Authors: Shachi Pranjal Vyas, Mark H Kaplan, Arman Kunwar Hansda, Ritobrata GoswamiAbstract:Vitamin D can modulate the innate and adaptive immune system. Vitamin D deficiency has been associated with various autoimmune diseases. Th9 Cells are implicated in the pathogenesis of numerous autoimmune diseases. Thus, we investigated the role of calcitriol (active metabolite of vitamin D) in the regulation of Th9 Cell differentiation. In this study, we have unraveled the molecular mechanisms of calcitriol-mediated regulation of Th9 Cell differentiation. Calcitriol significantly diminished IL-9 secretion from murine Th9 Cells associated with downregulated expression of the Th9-associated transcription factor, PU.1. Ectopic expression of VDR in Th9 Cells attenuated the percentage of IL-9-secreting Cells. VDR associated with PU.1 in Th9 Cells. Using a series of mutations, we were able to dissect the VDR domain involved in the regulation of the Il9 gene. The VDR-PU.1 interaction prevented the accessibility of PU.1 to the Il9 gene promoter, thereby restricting its expression. However, the expression of Foxp3, regulatory T Cell-specific transcription factor, was enhanced in the presence of calcitriol in Th9 Cells. When Th9 Cells are treated with both calcitriol and trichostatin A (histone deacetylase inhibitor), the level of IL-9 reached to the level of wild-type untreated Th9 Cells. Calcitriol attenuated specific histone acetylation at the Il9 gene. In contrast, calcitriol enhanced the recruitment of the histone modifier HDAC1 at the Il9 gene promoter. In summary, we have identified that calcitriol blocked the access of PU.1 to the Il9 gene by reducing its expression and associating with it as well as regulated the chromatin of the Il9 gene to regulate expression.
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The transcription factor network in Th9 Cells
Seminars in Immunopathology, 2017Co-Authors: Mark H KaplanAbstract:The development of T helper Cell subsets requires activated T Cells that respond to a polarizing cytokine environment resulting in the activation and expression of transcription factors. The subset-specific transcription factors bind and induce the production of specific effector cytokines. Th9 Cells express IL-9 and develop in the presence of TGFβ, IL-4, and IL-2. Each of these cytokines activates signaling pathways that are required for Th9 differentiation and IL-9 production. In this review, I summarize what is currently understood about the signaling pathways and transcription factors that promote the Th9 genetic program, providing some perspective for the integration of the signals in regulating the Il9 gene and dictating the expression of other Th9-associated genes. I highlight how experiments in mouse Cells have established a transcriptional network that is conserved in human T Cells and set the stage toward defining the next important questions for a more detailed understanding of Th9 Cell development and function.
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the ets family transcription factors etv5 and pu 1 function in parallel to promote Th9 Cell development
Journal of Immunology, 2016Co-Authors: Byunghee Koh, Duy Pham, Rukhsana Jabeen, Matthew R. Olson, Matthew M Hufford, Xin Sun, Mark H KaplanAbstract:The IL-9–secreting Th9 subset of CD4 Th Cells develop in response to an environment containing IL-4 and TGF-β, promoting allergic disease, autoimmunity, and resistance to pathogens. We previously identified a requirement for the ETS family transcription factor PU.1 in Th9 development. In this report, we demonstrate that the ETS transcription factor ETS variant 5 (ETV5) promotes IL-9 production in Th9 Cells by binding and recruiting histone acetyltransferases to the Il9 locus at sites distinct from PU.1. In Cells that are deficient in both PU.1 and ETV5 there is lower IL-9 production than in Cells lacking either factor alone. In vivo loss of PU.1 and ETV5 in T Cells results in distinct effects on allergic inflammation in the lung, suggesting that these factors function in parallel. Together, these data define a role for ETV5 in Th9 development and extend the paradigm of related transcription factors having complementary functions during differentiation.
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interleukin 9 is required for allergic airway inflammation mediated by the cytokine tslp
Immunity, 2013Co-Authors: Weiguo Yao, Yanlu Zhang, Rukhsana Jabeen, Evelyn T Nguyen, David S Wilkes, Robert S Tepper, Mark H Kaplan, Baohua ZhouAbstract:Thymic stromal lymphopoietin (TSLP) is an epithelial Cell-derived cytokine important for the initiation and development of T helper (Th2) Cell-mediated allergic inflammation. In this study, we identified a positive association between interleukin-9 (IL-9) and TSLP concentration in the serum of infants with atopic dermatitis. In primary Cell cultures, the addition of TSLP led to an increase in IL-9 production from human and mouse Th9 Cells, and induced an increase in signal transducer and activator of transcription 5 (STAT5) activation and binding to the Il9 promoter. In vivo, use of an adoptive transfer model demonstrated that TSLP promoted IL-9-dependent, Th9 Cell-induced allergic inflammation by acting directly on T Cells. Moreover, transgenic expression of TSLP in the lung stimulated IL-9 production in vivo, and anti-IL-9 treatment attenuated TSLP-induced airway inflammation. Together, our results demonstrate that TSLP promotes Th9 Cell differentiation and function and define a requirement for IL-9 in TSLP-induced allergic inflammation.
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The symphony of the ninth: the development and function of Th9 Cells
Current opinion in immunology, 2012Co-Authors: Rukhsana Jabeen, Mark H KaplanAbstract:CD4+ T helper Cells are obligate regulators of inflammatory disease. An expanding cadre of T helper (Th) subsets, specialized for promoting particular types of inflammation, function through the secretion of a restricted set of cytokines. The latest addition to the list of subsets is the Th9 Cell that secretes IL-9 as a signature cytokine and contributes to several classes of inflammatory disease. In this review we focus on recent advances in understanding the development of Th9 Cells, and how Th9 Cells contribute to the orchestration of disease.
Shachi Pranjal Vyas - One of the best experts on this subject based on the ideXlab platform.
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calcitriol attenuates tlr2 il 33 signaling pathway to repress Th9 Cell differentiation and potentially limits the pathophysiology of rheumatoid arthritis
Molecular and Cellular Biochemistry, 2021Co-Authors: Shachi Pranjal Vyas, Rajeshwar Nath Srivastava, Ritobrata GoswamiAbstract:There is limited information regarding the TLR2 signaling pathway involved in Th9 Cell differentiation. The role of calcitriol in regulating TLR2-mediated Th9 Cell development is unknown. Thus, we aimed to unravel the TLR2 signaling pathway in Th9 Cells and its regulation by calcitriol. We have used n = 5-6 animals for each murine experiment. Human studies involved five healthy volunteers. Moreover, ten healthy individuals and ten RA patients were included in the study. Murine and human Th9 Cells were treated with Calcitriol (100 nM) and Pam3CSK4 (2 µg/mL). The number of IL-9+ve Cells was determined by flow cytometry. Real-time PCR was used to assess the gene expression. Serum 25(OH)D3 levels were determined by HPLC. We observed that TLR2 signals via IL-33/ST2 in Th9 Cells. Increased TLR2 expression associated with increased IL9 expression and augmented disease severity in RA patients. Calcitriol attenuated TLR2 signaling in murine and human Th9 Cells. Low serum vitamin D3 level negatively associated with increased IL-9 and TLR2 expression and disease severity in RA patients. Our data suggest a potential role of calcitriol to ameliorate the disease severity of RA patients.
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Calcitriol attenuates TLR2/IL-33 signaling pathway to repress Th9 Cell differentiation and potentially limits the pathophysiology of rheumatoid arthritis
Molecular and Cellular Biochemistry, 2020Co-Authors: Shachi Pranjal Vyas, Rajeshwar Nath Srivastava, Ritobrata GoswamiAbstract:There is limited information regarding the TLR2 signaling pathway involved in Th9 Cell differentiation. The role of calcitriol in regulating TLR2-mediated Th9 Cell development is unknown. Thus, we aimed to unravel the TLR2 signaling pathway in Th9 Cells and its regulation by calcitriol. We have used n = 5–6 animals for each murine experiment. Human studies involved five healthy volunteers. Moreover, ten healthy individuals and ten RA patients were included in the study. Murine and human Th9 Cells were treated with Calcitriol (100 nM) and Pam_3CSK_4 (2 µg/mL). The number of IL-9+ve Cells was determined by flow cytometry. Real-time PCR was used to assess the gene expression. Serum 25(OH)D_3 levels were determined by HPLC. We observed that TLR2 signals via IL-33/ST2 in Th9 Cells. Increased TLR2 expression associated with increased IL9 expression and augmented disease severity in RA patients. Calcitriol attenuated TLR2 signaling in murine and human Th9 Cells. Low serum vitamin D3 level negatively associated with increased IL-9 and TLR2 expression and disease severity in RA patients. Our data suggest a potential role of calcitriol to ameliorate the disease severity of RA patients.
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Calcitriol Regulates the Differentiation of IL-9-Secreting Th9 Cells by Modulating the Transcription Factor PU.1.
Journal of immunology (Baltimore Md. : 1950), 2020Co-Authors: Shachi Pranjal Vyas, Mark H Kaplan, Arman Kunwar Hansda, Ritobrata GoswamiAbstract:Vitamin D can modulate the innate and adaptive immune system. Vitamin D deficiency has been associated with various autoimmune diseases. Th9 Cells are implicated in the pathogenesis of numerous autoimmune diseases. Thus, we investigated the role of calcitriol (active metabolite of vitamin D) in the regulation of Th9 Cell differentiation. In this study, we have unraveled the molecular mechanisms of calcitriol-mediated regulation of Th9 Cell differentiation. Calcitriol significantly diminished IL-9 secretion from murine Th9 Cells associated with downregulated expression of the Th9-associated transcription factor, PU.1. Ectopic expression of VDR in Th9 Cells attenuated the percentage of IL-9-secreting Cells. VDR associated with PU.1 in Th9 Cells. Using a series of mutations, we were able to dissect the VDR domain involved in the regulation of the Il9 gene. The VDR-PU.1 interaction prevented the accessibility of PU.1 to the Il9 gene promoter, thereby restricting its expression. However, the expression of Foxp3, regulatory T Cell-specific transcription factor, was enhanced in the presence of calcitriol in Th9 Cells. When Th9 Cells are treated with both calcitriol and trichostatin A (histone deacetylase inhibitor), the level of IL-9 reached to the level of wild-type untreated Th9 Cells. Calcitriol attenuated specific histone acetylation at the Il9 gene. In contrast, calcitriol enhanced the recruitment of the histone modifier HDAC1 at the Il9 gene promoter. In summary, we have identified that calcitriol blocked the access of PU.1 to the Il9 gene by reducing its expression and associating with it as well as regulated the chromatin of the Il9 gene to regulate expression.
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A Decade of Th9 Cells: Role of Th9 Cells in Inflammatory Bowel Disease.
Frontiers in immunology, 2018Co-Authors: Shachi Pranjal Vyas, Ritobrata GoswamiAbstract:T helper Cell subsets play a critical role in providing protection against offending pathogens by secreting specific cytokines. However, unrestrained T helper Cell responses can promote chronic inflammation-mediated inflammatory diseases. Dysregulated T helper Cell responses have been suggested to be involved in the pathogenesis of multiple inflammatory diseases, including allergic airway inflammation, rheumatoid arthritis, and inflammatory bowel disease (IBD) among others. Aberrant pro-inflammatory responses induced by Th1, Th2, and Th17 subsets are known to trigger IBD. IBD is a chronic inflammatory disease characterized by weight loss, diarrhea, pain, fever, and rectal bleeding. It poses a major health burden worldwide owing to the increased risk of colorectal cancer development. Despite numerous therapeutic advancements, IBD still remains a major health burden due to the inefficiency of the conventional therapies. Recently, IL-9-secreting Th9 Cells are known to be involved in the pathogenesis of IBD. However, the role of Th9 Cells and their secretory cytokine IL-9 in IBD is unclear. The functional relevance of Th9 Cells is also relatively understudied in IBD. Thus, investigating the actual role of various T helper Cell subsets including Th9 Cells in IBD is essential to develop novel therapies to treat IBD. Here, we highlight the role of Th9 Cells in promoting IBD. We discuss the mechanisms that might be employed by Th9 Cells and IL-9 in promoting IBD and thereby propose potential targets for the treatment of Th9 Cell-mediated IBD.
Rukhsana Jabeen - One of the best experts on this subject based on the ideXlab platform.
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Retroviral Transduction and Reporter Assay: Transcription Factor Cooperation in Th9 Cell Development.
Methods in molecular biology (Clifton N.J.), 2017Co-Authors: Rukhsana JabeenAbstract:Naive CD4+ T Cells differentiate into different T helper subsets in response to specific cytokine environment and transcription factors. Th9 Cells are induced in response to signals from cytokines, TGF-β and IL-4. Transcription factors that are downstream of these cytokines converge to drive the development of Th9 Cells. Retroviral transduction allows the genetic modification in T Cells thereby helping us to better understand the molecular mechanisms that control their development as well as function. In this chapter, an optimized protocol for retroviral transduction of murine Th9 Cells as well as transient transfection of Th9 Cells with luciferase reporter constructs is described.
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the ets family transcription factors etv5 and pu 1 function in parallel to promote Th9 Cell development
Journal of Immunology, 2016Co-Authors: Byunghee Koh, Duy Pham, Rukhsana Jabeen, Matthew R. Olson, Matthew M Hufford, Xin Sun, Mark H KaplanAbstract:The IL-9–secreting Th9 subset of CD4 Th Cells develop in response to an environment containing IL-4 and TGF-β, promoting allergic disease, autoimmunity, and resistance to pathogens. We previously identified a requirement for the ETS family transcription factor PU.1 in Th9 development. In this report, we demonstrate that the ETS transcription factor ETS variant 5 (ETV5) promotes IL-9 production in Th9 Cells by binding and recruiting histone acetyltransferases to the Il9 locus at sites distinct from PU.1. In Cells that are deficient in both PU.1 and ETV5 there is lower IL-9 production than in Cells lacking either factor alone. In vivo loss of PU.1 and ETV5 in T Cells results in distinct effects on allergic inflammation in the lung, suggesting that these factors function in parallel. Together, these data define a role for ETV5 in Th9 development and extend the paradigm of related transcription factors having complementary functions during differentiation.
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Th9 Cell development requires a BATF-regulated transcriptional network
The Journal of clinical investigation, 2013Co-Authors: Rukhsana Jabeen, Ritobrata Goswami, Evelyn T Nguyen, Olufolakemi Awe, Aishwarya Kulkarni, Andrea Attenasio, Daniel Walsh, Matthew R. Olson, Myung H. Kim, Robert S TepperAbstract:T helper 9 (Th9) Cells are specialized for the production of IL-9, promote allergic inflammation in mice, and are associated with allergic disease in humans. It has not been determined whether Th9 Cells express a characteristic transcriptional signature. In this study, we performed microarray analysis to identify genes enriched in Th9 Cells compared with other Th subsets. This analysis defined a transcriptional regulatory network required for the expression of a subset of Th9-enriched genes. The activator protein 1 (AP1) family transcription factor BATF (B Cell, activating transcription factor–like) was among the genes enriched in Th9 Cells and was required for the expression of IL-9 and other Th9-associated genes in both human and mouse T Cells. The expression of BATF was increased in Th9 cultures derived from atopic infants compared with Th9 cultures from control infants. T Cells deficient in BATF expression had a diminished capacity to promote allergic inflammation compared with wild-type controls. Moreover, mouse Th9 Cells ectopically expressing BATF were more efficient at promoting allergic inflammation than control transduced Cells. These data indicate that BATF is a central regulator of the Th9 phenotype and contributes to the development of allergic inflammation.
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interleukin 9 is required for allergic airway inflammation mediated by the cytokine tslp
Immunity, 2013Co-Authors: Weiguo Yao, Yanlu Zhang, Rukhsana Jabeen, Evelyn T Nguyen, David S Wilkes, Robert S Tepper, Mark H Kaplan, Baohua ZhouAbstract:Thymic stromal lymphopoietin (TSLP) is an epithelial Cell-derived cytokine important for the initiation and development of T helper (Th2) Cell-mediated allergic inflammation. In this study, we identified a positive association between interleukin-9 (IL-9) and TSLP concentration in the serum of infants with atopic dermatitis. In primary Cell cultures, the addition of TSLP led to an increase in IL-9 production from human and mouse Th9 Cells, and induced an increase in signal transducer and activator of transcription 5 (STAT5) activation and binding to the Il9 promoter. In vivo, use of an adoptive transfer model demonstrated that TSLP promoted IL-9-dependent, Th9 Cell-induced allergic inflammation by acting directly on T Cells. Moreover, transgenic expression of TSLP in the lung stimulated IL-9 production in vivo, and anti-IL-9 treatment attenuated TSLP-induced airway inflammation. Together, our results demonstrate that TSLP promotes Th9 Cell differentiation and function and define a requirement for IL-9 in TSLP-induced allergic inflammation.
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The symphony of the ninth: the development and function of Th9 Cells
Current opinion in immunology, 2012Co-Authors: Rukhsana Jabeen, Mark H KaplanAbstract:CD4+ T helper Cells are obligate regulators of inflammatory disease. An expanding cadre of T helper (Th) subsets, specialized for promoting particular types of inflammation, function through the secretion of a restricted set of cytokines. The latest addition to the list of subsets is the Th9 Cell that secretes IL-9 as a signature cytokine and contributes to several classes of inflammatory disease. In this review we focus on recent advances in understanding the development of Th9 Cells, and how Th9 Cells contribute to the orchestration of disease.
T L Denning - One of the best experts on this subject based on the ideXlab platform.
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IL-36γ signaling controls the induced regulatory T Cell–Th9 Cell balance via NFκB activation and STAT transcription factors
Mucosal Immunology, 2017Co-Authors: A Harusato, S W Yi, K Mitsutake, S Osuka, J E Kohlmeier, J D Li, A T Gewirtz, A Nusrat, T L DenningAbstract:Regulatory and effector T helper (Th) Cells are abundant at mucosal surfaces, especially in the intestine, where they control the critical balance between tolerance and inflammation. However, the key factors that reciprocally dictate differentiation along these specific lineages remain incompletely understood. Here we report that the interleukin-1 (IL-1) family member IL-36γ signals through IL-36 receptor, myeloid differentiation primary response gene 88, and nuclear factor-κBp50 in CD4^+ T Cells to potently inhibit Foxp3-expressing induced regulatory T Cell (T_reg) development, while concomitantly promoting the differentiation of Th9 Cells via a IL-2-STAT5- (signal transducer and activator of transcription factor 5) and IL-4-STAT6-dependent pathway. Consistent with these findings, mice deficient in IL-36γ were protected from Th Cell–driven intestinal inflammation and exhibited increased colonic T_reg Cells and diminished Th9 Cells. Our findings thus reveal a fundamental contribution for the IL-36/IL-36R axis in regulating the T_reg–Th9 Cell balance with broad implications for Th Cell–mediated disorders, such as inflammatory bowel diseases and particularly ulcerative colitis.
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il 36γ signaling controls the induced regulatory t Cell Th9 Cell balance via nfκb activation and stat transcription factors
Mucosal Immunology, 2017Co-Authors: A Harusato, K Mitsutake, S Osuka, J E Kohlmeier, A T Gewirtz, A Nusrat, Hirohito Abo, Vu Ngo, T L DenningAbstract:Regulatory and effector T helper (Th) Cells are abundant at mucosal surfaces, especially in the intestine, where they control the critical balance between tolerance and inflammation. However, the key factors that reciprocally dictate differentiation along these specific lineages remain incompletely understood. Here we report that the interleukin-1 (IL-1) family member IL-36γ signals through IL-36 receptor, myeloid differentiation primary response gene 88, and nuclear factor-κBp50 in CD4+ T Cells to potently inhibit Foxp3-expressing induced regulatory T Cell (Treg) development, while concomitantly promoting the differentiation of Th9 Cells via a IL-2-STAT5- (signal transducer and activator of transcription factor 5) and IL-4-STAT6-dependent pathway. Consistent with these findings, mice deficient in IL-36γ were protected from Th Cell-driven intestinal inflammation and exhibited increased colonic Treg Cells and diminished Th9 Cells. Our findings thus reveal a fundamental contribution for the IL-36/IL-36R axis in regulating the Treg-Th9 Cell balance with broad implications for Th Cell-mediated disorders, such as inflammatory bowel diseases and particularly ulcerative colitis.