The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Westley H Reeves - One of the best experts on this subject based on the ideXlab platform.
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maintenance of anti sm rnp autoantibody production by plasma cells residing in ectopic lymphoid tissue and bone marrow memory b cells
Journal of Immunology, 2013Co-Authors: Jason S Weinstein, Dina C Nacionales, Pui Y Lee, Kindra M Kellyscumpia, Eric S Sobel, Matthew J Delano, Philip O Scumpia, Lijun Yang, Lyle L Moldawer, Westley H ReevesAbstract:Although ectopic lymphoid tissue formation is associated with many autoimmune diseases, it is unclear whether it serves a functional role in autoimmune responses. 2,6,10,14-Tetramethylpentadecane causes chronic peritoneal inflammation and lupus-like disease with autoantibody production and ectopic lymphoid tissue (Lipogranuloma) formation. A novel transplantation model was used to show that transplanted Lipogranulomas retain their lymphoid structure over a prolonged period in the absence of chronic peritoneal inflammation. Recipients of transplanted Lipogranulomas produced anti-U1A autoantibodies derived exclusively from the donor, despite nearly complete repopulation of the transplanted Lipogranulomas by host lymphocytes. The presence of ectopic lymphoid tissue alone was insufficient, as an anti-U1A response was not generated by the host in the absence of ongoing peritoneal inflammation. Donor-derived anti-U1A autoantibodies were produced for up to 2 mo by plasma cells/plasmablasts recruited to the ectopic lymphoid tissue by CXCR4. Although CD4 + T cells were not required for autoantibody production from the transplanted Lipogranulomas, de novo generation of anti-U1A plasma cells/plasmablasts was reduced following T cell depletion. Significantly, a population of memory B cells was identified in the bone marrow and spleen that did not produce anti-U1A autoantibodies unless stimulated by LPS to undergo terminal differentiation. We conclude that 2,6,10,14-tetramethylpentadecane promotes the T cell–dependent development of class-switched, autoreactive memory B cells and plasma cells/plasmablasts. The latter home to ectopic lymphoid tissue and continue to produce autoantibodies after transplantation and in the absence of peritoneal inflammation. However, peritoneal inflammation appears necessary to generate autoreactive B cells de novo.
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b cell proliferation somatic hypermutation class switch recombination and autoantibody production in ectopic lymphoid tissue in murine lupus
Journal of Immunology, 2009Co-Authors: Dina C Nacionales, Jason S Weinstein, Xiaojie Yan, Emilia Albesiano, Pui Y Lee, Kindra M Kellyscumpia, Robert Lyons, Minoru Satoh, Nicholas Chiorazzi, Westley H ReevesAbstract:Intraperitoneal exposure of nonautoimmune mice to 2,6,10,14-tetramethylpentadecane (TMPD) causes lupus and the formation of ectopic lymphoid tissue. Although associated with humoral autoimmunity, it is not known whether Ab responses develop within ectopic lymphoid tissue or if B cells only secondarily migrate there. We show that ectopic lymphoid tissue induced by TMPD not only resembles secondary lymphoid tissue morphologically, but it also displays characteristics of germinal center reactions. Proliferating T and B lymphocytes were found within ectopic lymphoid tissue, activation-induced cytidine deaminase was expressed, and class-switched B cells were present. The presence of circular DNA intermediates, a hallmark of active class switch recombination, suggested that class switching occurs within the ectopic lymphoid tissue. Individual collections of ectopic lymphoid tissue ("Lipogranulomas") from the same mouse contained different B cell repertoires, consistent with local germinal center-like reactions. Class-switched anti-RNP autoantibody-producing cells were also found in the Lipogranulomas. Somatic hypermutation in the Lipogranulomas was T cell-dependent, as was the production of isotype-switched anti-Sm/RNP autoantibodies. Thus, ectopic lymphoid tissue induced by TMPD recapitulates many of the functional characteristics of secondary lymphoid tissue and contains autoantibody-secreting cells, which may escape from normal censoring mechanisms in this location.
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type i interferon production by tertiary lymphoid tissue developing in response to 2 6 10 14 tetramethyl pentadecane pristane
American Journal of Pathology, 2006Co-Authors: Dina C Nacionales, Jason S Weinstein, Minoru Satoh, Kindra M Kelly, Haoyang Zhuang, Yi Li, Eric S Sobel, Yoshiki Kuroda, Jun Akaogi, Westley H ReevesAbstract:Lymphoid neogenesis is associated with antibody-mediated autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. Although systemic lupus erythematosus is the prototypical B-cell-mediated autoimmune disease, the role of lymphoid neogenesis in its pathogenesis is unknown. Intraperitoneal injection of 2,6,10,14-tetramethyl-pentadecane (TMPD, pristane) or mineral oil causes Lipogranuloma formation in mice, but only TMPD-treated mice develop lupus. We report that Lipogranulomas are a form of lymphoid neogenesis. Immunoperoxidase staining of Lipogranulomas revealed B cells, CD4 + T cells, and dendritic cells and in some cases organization into T- and B-cell zones. Lipogranulomas also expressed the lymphoid chemokines CCL21, CCL19, CXCL13, CXCL12, and CCL22. Expression of the type I interferon (IFN-I)-inducible genes Mx1 , IRF7 , IP-10 , and ISG-15 was greatly increased in TMPD- versus mineral oil-induced Lipogranulomas. Dendritic cells from TMPD Lipogranulomas underwent activation/maturation with high CD86 and interleukin-12 expression. Magnetic bead depletion of dendritic cells markedly diminished IFN-inducible gene ( Mx1 ) expression. We conclude that TMPD-induced lupus is associated with the formation of ectopic lymphoid tissue containing activated dendritic cells producing IFN-I and interleukin-12. In view of the increased IFN-I production in systemic lupus erythematosus, these studies suggest that IFN-I from ectopic lymphoid tissue could play a role in the pathogenesis of experimental lupus in mice.
Dina C Nacionales - One of the best experts on this subject based on the ideXlab platform.
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maintenance of anti sm rnp autoantibody production by plasma cells residing in ectopic lymphoid tissue and bone marrow memory b cells
Journal of Immunology, 2013Co-Authors: Jason S Weinstein, Dina C Nacionales, Pui Y Lee, Kindra M Kellyscumpia, Eric S Sobel, Matthew J Delano, Philip O Scumpia, Lijun Yang, Lyle L Moldawer, Westley H ReevesAbstract:Although ectopic lymphoid tissue formation is associated with many autoimmune diseases, it is unclear whether it serves a functional role in autoimmune responses. 2,6,10,14-Tetramethylpentadecane causes chronic peritoneal inflammation and lupus-like disease with autoantibody production and ectopic lymphoid tissue (Lipogranuloma) formation. A novel transplantation model was used to show that transplanted Lipogranulomas retain their lymphoid structure over a prolonged period in the absence of chronic peritoneal inflammation. Recipients of transplanted Lipogranulomas produced anti-U1A autoantibodies derived exclusively from the donor, despite nearly complete repopulation of the transplanted Lipogranulomas by host lymphocytes. The presence of ectopic lymphoid tissue alone was insufficient, as an anti-U1A response was not generated by the host in the absence of ongoing peritoneal inflammation. Donor-derived anti-U1A autoantibodies were produced for up to 2 mo by plasma cells/plasmablasts recruited to the ectopic lymphoid tissue by CXCR4. Although CD4 + T cells were not required for autoantibody production from the transplanted Lipogranulomas, de novo generation of anti-U1A plasma cells/plasmablasts was reduced following T cell depletion. Significantly, a population of memory B cells was identified in the bone marrow and spleen that did not produce anti-U1A autoantibodies unless stimulated by LPS to undergo terminal differentiation. We conclude that 2,6,10,14-tetramethylpentadecane promotes the T cell–dependent development of class-switched, autoreactive memory B cells and plasma cells/plasmablasts. The latter home to ectopic lymphoid tissue and continue to produce autoantibodies after transplantation and in the absence of peritoneal inflammation. However, peritoneal inflammation appears necessary to generate autoreactive B cells de novo.
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b cell proliferation somatic hypermutation class switch recombination and autoantibody production in ectopic lymphoid tissue in murine lupus
Journal of Immunology, 2009Co-Authors: Dina C Nacionales, Jason S Weinstein, Xiaojie Yan, Emilia Albesiano, Pui Y Lee, Kindra M Kellyscumpia, Robert Lyons, Minoru Satoh, Nicholas Chiorazzi, Westley H ReevesAbstract:Intraperitoneal exposure of nonautoimmune mice to 2,6,10,14-tetramethylpentadecane (TMPD) causes lupus and the formation of ectopic lymphoid tissue. Although associated with humoral autoimmunity, it is not known whether Ab responses develop within ectopic lymphoid tissue or if B cells only secondarily migrate there. We show that ectopic lymphoid tissue induced by TMPD not only resembles secondary lymphoid tissue morphologically, but it also displays characteristics of germinal center reactions. Proliferating T and B lymphocytes were found within ectopic lymphoid tissue, activation-induced cytidine deaminase was expressed, and class-switched B cells were present. The presence of circular DNA intermediates, a hallmark of active class switch recombination, suggested that class switching occurs within the ectopic lymphoid tissue. Individual collections of ectopic lymphoid tissue ("Lipogranulomas") from the same mouse contained different B cell repertoires, consistent with local germinal center-like reactions. Class-switched anti-RNP autoantibody-producing cells were also found in the Lipogranulomas. Somatic hypermutation in the Lipogranulomas was T cell-dependent, as was the production of isotype-switched anti-Sm/RNP autoantibodies. Thus, ectopic lymphoid tissue induced by TMPD recapitulates many of the functional characteristics of secondary lymphoid tissue and contains autoantibody-secreting cells, which may escape from normal censoring mechanisms in this location.
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type i interferon production by tertiary lymphoid tissue developing in response to 2 6 10 14 tetramethyl pentadecane pristane
American Journal of Pathology, 2006Co-Authors: Dina C Nacionales, Jason S Weinstein, Minoru Satoh, Kindra M Kelly, Haoyang Zhuang, Yi Li, Eric S Sobel, Yoshiki Kuroda, Jun Akaogi, Westley H ReevesAbstract:Lymphoid neogenesis is associated with antibody-mediated autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. Although systemic lupus erythematosus is the prototypical B-cell-mediated autoimmune disease, the role of lymphoid neogenesis in its pathogenesis is unknown. Intraperitoneal injection of 2,6,10,14-tetramethyl-pentadecane (TMPD, pristane) or mineral oil causes Lipogranuloma formation in mice, but only TMPD-treated mice develop lupus. We report that Lipogranulomas are a form of lymphoid neogenesis. Immunoperoxidase staining of Lipogranulomas revealed B cells, CD4 + T cells, and dendritic cells and in some cases organization into T- and B-cell zones. Lipogranulomas also expressed the lymphoid chemokines CCL21, CCL19, CXCL13, CXCL12, and CCL22. Expression of the type I interferon (IFN-I)-inducible genes Mx1 , IRF7 , IP-10 , and ISG-15 was greatly increased in TMPD- versus mineral oil-induced Lipogranulomas. Dendritic cells from TMPD Lipogranulomas underwent activation/maturation with high CD86 and interleukin-12 expression. Magnetic bead depletion of dendritic cells markedly diminished IFN-inducible gene ( Mx1 ) expression. We conclude that TMPD-induced lupus is associated with the formation of ectopic lymphoid tissue containing activated dendritic cells producing IFN-I and interleukin-12. In view of the increased IFN-I production in systemic lupus erythematosus, these studies suggest that IFN-I from ectopic lymphoid tissue could play a role in the pathogenesis of experimental lupus in mice.
Neil D. Theise - One of the best experts on this subject based on the ideXlab platform.
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Hepatic Lipogranulomas in patients with chronic liver disease: Association with hepatitis C and fatty liver disease
World journal of gastroenterology, 2010Co-Authors: Hongfa Zhu, Henry C. Bodenheimer, David J. Clain, Albert D. Min, Neil D. TheiseAbstract:AIM: To study the significance and clinical implication of hepatic Lipogranuloma in chronic liver diseases, including fatty liver disease and hepatitis C. METHODS: A total of 376 sequential, archival liver biopsy specimens were reviewed. Lipogranuloma, steatosis and steato-fibrosis were evaluated with combined hematoxylin and eosin and Masson’s trichrome staining. RESULTS: Fifty-eight (15.4%) patients had Lipogranuloma, including 46 patients with hepatitis C, 14 patients with fatty liver disease, and 5 patients with other diseases. Hepatic Lipogranuloma was more frequently seen in patients with hepatitis C (21%) and fatty liver disease (18%), and its incidence was significantly higher than that in control group (P < 0.0002 and P < 0.007, respectively). In addition, 39 out of the 58 patients with Lipogranuloma were associated with steatosis and/or steato-fibrosis. Of the 18 Lipogranuloma patients with clinical information available for review, 15 (83%) had risk factors associated with fatty liver disease, such as alcohol use, obesity, hyperlipidemia, and diabetes mellitus. Although the incidence of these risk factors was greater in patients with Lipogranuloma than in control group (60%), it did not reach statistical significance. CONCLUSION: Hepatic Lipogranuloma is not limited to mineral oil use and commonly associated with hepatic steatosis, hepatitis C and fatty liver disease. With additional histological features of steato-fibrosis, Lipogranuloma can also be used as a marker of prior hepatic steatosis.
Jason S Weinstein - One of the best experts on this subject based on the ideXlab platform.
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maintenance of anti sm rnp autoantibody production by plasma cells residing in ectopic lymphoid tissue and bone marrow memory b cells
Journal of Immunology, 2013Co-Authors: Jason S Weinstein, Dina C Nacionales, Pui Y Lee, Kindra M Kellyscumpia, Eric S Sobel, Matthew J Delano, Philip O Scumpia, Lijun Yang, Lyle L Moldawer, Westley H ReevesAbstract:Although ectopic lymphoid tissue formation is associated with many autoimmune diseases, it is unclear whether it serves a functional role in autoimmune responses. 2,6,10,14-Tetramethylpentadecane causes chronic peritoneal inflammation and lupus-like disease with autoantibody production and ectopic lymphoid tissue (Lipogranuloma) formation. A novel transplantation model was used to show that transplanted Lipogranulomas retain their lymphoid structure over a prolonged period in the absence of chronic peritoneal inflammation. Recipients of transplanted Lipogranulomas produced anti-U1A autoantibodies derived exclusively from the donor, despite nearly complete repopulation of the transplanted Lipogranulomas by host lymphocytes. The presence of ectopic lymphoid tissue alone was insufficient, as an anti-U1A response was not generated by the host in the absence of ongoing peritoneal inflammation. Donor-derived anti-U1A autoantibodies were produced for up to 2 mo by plasma cells/plasmablasts recruited to the ectopic lymphoid tissue by CXCR4. Although CD4 + T cells were not required for autoantibody production from the transplanted Lipogranulomas, de novo generation of anti-U1A plasma cells/plasmablasts was reduced following T cell depletion. Significantly, a population of memory B cells was identified in the bone marrow and spleen that did not produce anti-U1A autoantibodies unless stimulated by LPS to undergo terminal differentiation. We conclude that 2,6,10,14-tetramethylpentadecane promotes the T cell–dependent development of class-switched, autoreactive memory B cells and plasma cells/plasmablasts. The latter home to ectopic lymphoid tissue and continue to produce autoantibodies after transplantation and in the absence of peritoneal inflammation. However, peritoneal inflammation appears necessary to generate autoreactive B cells de novo.
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b cell proliferation somatic hypermutation class switch recombination and autoantibody production in ectopic lymphoid tissue in murine lupus
Journal of Immunology, 2009Co-Authors: Dina C Nacionales, Jason S Weinstein, Xiaojie Yan, Emilia Albesiano, Pui Y Lee, Kindra M Kellyscumpia, Robert Lyons, Minoru Satoh, Nicholas Chiorazzi, Westley H ReevesAbstract:Intraperitoneal exposure of nonautoimmune mice to 2,6,10,14-tetramethylpentadecane (TMPD) causes lupus and the formation of ectopic lymphoid tissue. Although associated with humoral autoimmunity, it is not known whether Ab responses develop within ectopic lymphoid tissue or if B cells only secondarily migrate there. We show that ectopic lymphoid tissue induced by TMPD not only resembles secondary lymphoid tissue morphologically, but it also displays characteristics of germinal center reactions. Proliferating T and B lymphocytes were found within ectopic lymphoid tissue, activation-induced cytidine deaminase was expressed, and class-switched B cells were present. The presence of circular DNA intermediates, a hallmark of active class switch recombination, suggested that class switching occurs within the ectopic lymphoid tissue. Individual collections of ectopic lymphoid tissue ("Lipogranulomas") from the same mouse contained different B cell repertoires, consistent with local germinal center-like reactions. Class-switched anti-RNP autoantibody-producing cells were also found in the Lipogranulomas. Somatic hypermutation in the Lipogranulomas was T cell-dependent, as was the production of isotype-switched anti-Sm/RNP autoantibodies. Thus, ectopic lymphoid tissue induced by TMPD recapitulates many of the functional characteristics of secondary lymphoid tissue and contains autoantibody-secreting cells, which may escape from normal censoring mechanisms in this location.
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type i interferon production by tertiary lymphoid tissue developing in response to 2 6 10 14 tetramethyl pentadecane pristane
American Journal of Pathology, 2006Co-Authors: Dina C Nacionales, Jason S Weinstein, Minoru Satoh, Kindra M Kelly, Haoyang Zhuang, Yi Li, Eric S Sobel, Yoshiki Kuroda, Jun Akaogi, Westley H ReevesAbstract:Lymphoid neogenesis is associated with antibody-mediated autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. Although systemic lupus erythematosus is the prototypical B-cell-mediated autoimmune disease, the role of lymphoid neogenesis in its pathogenesis is unknown. Intraperitoneal injection of 2,6,10,14-tetramethyl-pentadecane (TMPD, pristane) or mineral oil causes Lipogranuloma formation in mice, but only TMPD-treated mice develop lupus. We report that Lipogranulomas are a form of lymphoid neogenesis. Immunoperoxidase staining of Lipogranulomas revealed B cells, CD4 + T cells, and dendritic cells and in some cases organization into T- and B-cell zones. Lipogranulomas also expressed the lymphoid chemokines CCL21, CCL19, CXCL13, CXCL12, and CCL22. Expression of the type I interferon (IFN-I)-inducible genes Mx1 , IRF7 , IP-10 , and ISG-15 was greatly increased in TMPD- versus mineral oil-induced Lipogranulomas. Dendritic cells from TMPD Lipogranulomas underwent activation/maturation with high CD86 and interleukin-12 expression. Magnetic bead depletion of dendritic cells markedly diminished IFN-inducible gene ( Mx1 ) expression. We conclude that TMPD-induced lupus is associated with the formation of ectopic lymphoid tissue containing activated dendritic cells producing IFN-I and interleukin-12. In view of the increased IFN-I production in systemic lupus erythematosus, these studies suggest that IFN-I from ectopic lymphoid tissue could play a role in the pathogenesis of experimental lupus in mice.
Hongfa Zhu - One of the best experts on this subject based on the ideXlab platform.
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Hepatic Lipogranulomas in patients with chronic liver disease: Association with hepatitis C and fatty liver disease
World journal of gastroenterology, 2010Co-Authors: Hongfa Zhu, Henry C. Bodenheimer, David J. Clain, Albert D. Min, Neil D. TheiseAbstract:AIM: To study the significance and clinical implication of hepatic Lipogranuloma in chronic liver diseases, including fatty liver disease and hepatitis C. METHODS: A total of 376 sequential, archival liver biopsy specimens were reviewed. Lipogranuloma, steatosis and steato-fibrosis were evaluated with combined hematoxylin and eosin and Masson’s trichrome staining. RESULTS: Fifty-eight (15.4%) patients had Lipogranuloma, including 46 patients with hepatitis C, 14 patients with fatty liver disease, and 5 patients with other diseases. Hepatic Lipogranuloma was more frequently seen in patients with hepatitis C (21%) and fatty liver disease (18%), and its incidence was significantly higher than that in control group (P < 0.0002 and P < 0.007, respectively). In addition, 39 out of the 58 patients with Lipogranuloma were associated with steatosis and/or steato-fibrosis. Of the 18 Lipogranuloma patients with clinical information available for review, 15 (83%) had risk factors associated with fatty liver disease, such as alcohol use, obesity, hyperlipidemia, and diabetes mellitus. Although the incidence of these risk factors was greater in patients with Lipogranuloma than in control group (60%), it did not reach statistical significance. CONCLUSION: Hepatic Lipogranuloma is not limited to mineral oil use and commonly associated with hepatic steatosis, hepatitis C and fatty liver disease. With additional histological features of steato-fibrosis, Lipogranuloma can also be used as a marker of prior hepatic steatosis.