The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Hajime Karasuyama - One of the best experts on this subject based on the ideXlab platform.
-
multifaceted roles of Basophils in health and disease
The Journal of Allergy and Clinical Immunology, 2017Co-Authors: Hajime Karasuyama, Kensuke Miyake, Soichiro Yoshikawa, Yoshinori YamanishiAbstract:Until recently, Basophils had often been neglected in immunologic studies because of their minority status among immune cells or confused with tissue-resident mast cells because of some phenotypic similarities between them in spite of different anatomic localization. It is now appreciated that Basophils and mast cells are distinct cell lineages and that Basophils play important and nonredundant roles distinct from those played by mast cells. On the one hand, Basophils contribute beneficially to protective immunity, particularly against parasitic infections. On the other hand, Basophils are involved in the development of various disorders, including allergy and autoimmune disease. Basophils interact with other immune cells and nonhematopoietic cells through cell-to-cell contact or basophil-derived factors, such as cytokines and proteases, contributing to the regulation of immune and allergic responses. In this review article we highlight recent advances in our understanding of basophil pathophysiology in human subjects and animal models by consolidating research findings reported during the past 5 years. Further studies on Basophils and their products will help identify suitable targets for novel therapeutics in allergy and effective vaccines against parasitic infection.
-
Basophils contribute to pristane induced lupus like nephritis model
Scientific Reports, 2017Co-Authors: Barbara Dema, Yasmine Lamri, Christophe Pellefigues, Emeline Pacreau, Fanny Saidoune, Caroline Bidault, Hajime Karasuyama, Karim Sacre, Eric Daugas, Nicolas CharlesAbstract:Lupus nephritis (LN), one of the most severe outcomes of systemic lupus erythematosus (SLE), is initiated by glomerular deposition of immune-complexes leading to an inflammatory response and kidney failure. Autoantibodies to nuclear antigens and autoreactive B and T cells are central in SLE pathogenesis. Immune mechanisms amplifying this autoantibody production drive flares of the disease. We previously showed that Basophils were contributing to LN development in a spontaneous lupus-like mouse model (constitutive Lyn −/− mice) and in SLE subjects through their activation and migration to secondary lymphoid organs (SLOs) where they amplify autoantibody production. In order to study the basophil-specific mechanisms by which these cells contribute to LN development, we needed to validate their involvement in a genetically independent SLE-like mouse model. Pristane, when injected to non-lupus-prone mouse strains, induces a LN-like disease. In this inducible model, Basophils were activated and accumulated in SLOs to promote autoantibody production. Basophil depletion by two distinct approaches dampened LN-like disease, demonstrating their contribution to the pristane-induced LN model. These results enable further studies to decipher molecular mechanisms by which Basophils contribute to lupus progression.
-
Emerging roles of Basophils in allergic inflammation
Allergology International, 2017Co-Authors: Kensuke Miyake, Hajime KarasuyamaAbstract:Basophils have long been neglected in immunological studies because they were regarded as only minor relatives of mast cells. However, recent advances in analytical tools for Basophils have clarified the non-redundant roles of Basophils in allergic inflammation. Basophils play crucial roles in both IgE-dependent and -independent allergic inflammation, through their migration to the site of inflammation and secretion of various mediators, including cytokines, chemokines, and proteases. Basophils are known to produce large amounts of IL-4 in response to various stimuli. Basophil-derived IL-4 has recently been shown to play versatile roles in allergic inflammation by acting on various cell types, including macrophages, innate lymphoid cells, fibroblasts, and endothelial cells. Basophil-derived serine proteases are also crucial for the aggravation of allergic inflammation. Moreover, recent reports suggest the roles of Basophils in modulating adaptive immune responses, particularly in the induction of Th2 differentiation and enhancement of humoral memory responses. In this review, we will discuss recent advances in understanding the roles of Basophils in allergic inflammation.
-
nadph oxidase independent formation of extracellular dna traps by Basophils
Journal of Immunology, 2014Co-Authors: Md Mahbubul Morshed, Hajime Karasuyama, Andrew F Walls, Kazushige Obataninomiya, Ruslan Hlushchuk, Dagmar Simon, Valentin Djonov, Alexander Eggel, Thomas Kaufmann, Hansuwe SimonAbstract:Basophils are primarily associated with a proinflammatory and immunoregulatory role in allergic diseases and parasitic infections. Recent studies have shown that Basophils can also bind various bacteria both in the presence and the absence of opsonizing Abs. In this report, we show that both human and mouse Basophils are able to produce mitochondrial reactive oxygen species and to form extracellular DNA traps upon IL-3 priming and subsequent activation of the complement factor 5 a receptor or FceRI. Such basophil extracellular traps (BETs) contain mitochondrial, but not nuclear DNA, as well as the granule proteins basogranulin and mouse mast cell protease 8. BET formation occurs despite the absence of any functional NADPH oxidase in Basophils. BETs can be found in both human and mouse inflamed tissues, suggesting that they also play a role under in vivo inflammatory conditions. Taken together, these findings suggest that Basophils exert direct innate immune effector functions in the extracellular space.
-
gata 1 regulates the generation and function of Basophils
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Kazushige Obataninomiya, Susumu Nakae, Hidemitsu Tsutsui, Kenji Ishiwata, Masayuki Miyasaka, Kenji Matsumoto, Hirotaka Kanuka, Naohiko Inase, Hajime KarasuyamaAbstract:Developmental processes of hematopoietic cells are orchestrated by transcriptional networks. GATA-1, the founding member of the GATA family of transcription factors, has been demonstrated to play crucial roles in the differentiation of erythroid cells, magakaryocytes, eosinophils, and mast cells. However, the role of GATA-1 in Basophils remains elusive. Here we show that Basophils abundantly express Gata1 mRNAs, and that siRNA-mediated knockdown of Gata1 resulted in impaired production of IL-4 by Basophils in response to the stimulation with IgE plus antigens. ΔdblGATA mice that carry the mutated Gata1 promoter and are widely used for functional analysis of eosinophils owing to their selective loss of eosinophils showed a decreased number of Basophils with reduced expression of Gata1 mRNAs. The number of basophil progenitors in bone marrow was reduced in these mice, and the generation of Basophils from their bone marrow cells in culture with IL-3 or thymic stromal lymphopoietin was impaired. ΔdblGATA Basophils responded poorly ex vivo to stimulation with IgE plus antigens compared with wild-type Basophils as assessed by degranulation and production of IL-4 and IL-6. Moreover, ΔdblGATA mice showed impaired responses in basophil-mediated protective immunity against intestinal helminth infection. Thus, ΔdblGATA mice showed numerical and functional aberrancy in Basophils in addition to the known deficiency of eosinophils. Our findings demonstrate that GATA-1 plays a key role in the generation and function of Basophils and underscore the need for careful distinction of the cell lineage responsible for each phenotype observed in ΔdblGATA mice.
Haruka Sasaki - One of the best experts on this subject based on the ideXlab platform.
-
transcription factor irf8 plays a critical role in the development of murine Basophils and mast cells
Blood, 2015Co-Authors: Haruka Sasaki, Daisuke Kurotaki, Shinichi Koizumi, Hongsheng Wang, Naoki Osato, Izumi Sasaki, Chika Kaneda, Hideaki Sato, Akira Nishiyama, Tsuneyasu KaishoAbstract:Basophils and mast cells play critical roles in host defense against pathogens and allergic disorders. However, the molecular mechanism by which these cells are generated is not completely understood. Here we demonstrate that interferon regulatory factor-8 (IRF8), a transcription factor essential for the development of several myeloid lineages, also regulates basophil and mast cell development. Irf8−/− mice displayed a severe reduction in basophil counts, which was accounted for by the absence of pre-basophil and mast cell progenitors (pre-BMPs). Although Irf8−/− mice retained peripheral tissue mast cells, remaining progenitors from Irf8−/− mice including granulocyte progenitors (GPs) were unable to efficiently generate either Basophils or mast cells, indicating that IRF8 also contributes to the development of mast cells. IRF8 appeared to function at the GP stage, because IRF8 was expressed in GPs, but not in Basophils, mast cells, and basophil/mast cell-restricted progenitor cells. Furthermore, we demonstrate that GATA2, a transcription factor known to promote basophil and mast cell differentiation, acts downstream of IRF8. These results shed light on the pathways and mechanism underlying the development of Basophils and mast cells.
-
the transcription factor irf8 is a key transcription factor for basophil development
Blood, 2013Co-Authors: Haruka Sasaki, Naoki Osato, Izumi Sasaki, Chika Kaneda, Herbert C. Morse, Tsuneyasu Kaisho, Hideaki Sato, Akira Nishiyama, Hiroyuki Aburatani, Keiko OzatoAbstract:Basophils are the rarest granulocytes circulating in the peripheral blood. They play critical roles in anti-parasite Th2-type immune responses and chronic allergic disorders. The developmental pathway for Basophils has been recently demonstrated; myeloid progenitors pass through common myeloid progenitors, granulocyte-monocyte progenitors, granulocyte-committed progenitors (GPs), and basophil-committed progenitors (BaPs) in the bone marrow. BaPs then give rise to mature Basophils. However, our understanding of how this pathway is regulated remains still elusive. Interferon Regulatory Factor-8 (IRF8), a hematopoietic cell-specific IRF transcription factor, is essential for the development of monocytes, dendritic cells, and eosinophils, while it inhibits neutrophil differentiation. Its role in the development of Basophils has yet to be analyzed. In this study, we investigated whether IRF8 has any role in the development of the basophil lineage. We found that Irf8 –/– mice displayed a severe reduction of basophil counts in the bone marrow, peripheral blood and spleen compared to wild-type (WT) mice. Irf8 –/– mice retained GPs but lacked BaPs. Cell transfer experiments revealed that the defect of basophil development in Irf8 –/– mice resides in bone marrow cells. We utilized IRF8-GFP chimera knock-in mice to examine IRF8 protein expression in the basophil lineage at a single cell level. We found that GPs, but not BaPs and mature Basophils, expressed IRF8. Furthermore, purified Irf8 –/– GPs failed to efficiently give rise to Basophils in vitro . These results indicate that IRF8 acts at the stage of GPs in a cell-intrinsic manner. To understand the mechanism by which IRF8 promotes basophil development, we performed transcriptome analysis of purified GPs from WT and Irf8 –/– mice by microarray. Because IRF8 is no more expressed in BaPs, we envisaged that IRF8 acts by inducing downstream transcription factors in GPs. The expression of several transcription factor genes such as Gata2 and Spib was reduced in Irf8 –/– GPs compared to WT GPs. Analysis of DNA motifs in the promoter regions of genes downregulated in Irf8 –/– GPs predicted that GATA transcription factor(s) may act downstream of IRF8. Indeed, retroviral transduction of GATA2, known to be essential for basophil development, into Irf8 –/– hematopoietic progenitor cells rescued basophil differentiation in vitro . On the other hand, Spib –/– mice showed no obvious defects in basophil development. Taken together, these results suggest that the IRF8-GATA2 axis in GPs critically regulates basophil development. Disclosures: No relevant conflicts of interest to declare.
-
226 the transcription factor irf8 is required for the development of Basophils
Cytokine, 2013Co-Authors: Haruka Sasaki, Daisuke Kurotak, Keiko Ozato, Herbert C. Morse, Hideaki Sato, Tomohiko TamuraAbstract:Basophils are the rarest granulocytes circulating in the peripheral blood. Although their non-redundant roles in Th2-type immunity and allergic disorders have been clarified, little is known about the pathways and regulators of their development. Interferon Regulatory Factor-8 (IRF8) is a transcription factor known to promote the development of monocytes/macrophages and dendritic cells while inhibiting that of neutrophils. In this report, we show that this transcription factor is required for the development of the basophil lineage. Irf8−/− mice display a severe reduction of basophil counts in the bone marrow, peripheral blood and spleen. Bone marrow transfer experiments showed that IRF8 functions in a bone marrow cell-intrinsic manner. Analysis of bone marrow progenitors revealed that the number of granulocyte-committed progenitors (GPs) in Irf8−/− mice is comparable to that of wild-type mice, while that of basophil-committed progenitors (BaPs) is diminished. Using IRF8-GFP knock-in mice, we found that GPs but not BaPs and mature Basophils express IRF8, suggesting that IRF8 may act in the stage of GPs. Indeed, GPs purified from Irf8−/− mice failed to efficiently give rise to Basophils in vitro in the presence of IL-3. Taken together, these results uncover a previously unrecognized role of IRF8 in granulocyte development.
Jeanpaul Latge - One of the best experts on this subject based on the ideXlab platform.
-
correction corrigendum circulating human Basophils lack the features of professional antigen presenting cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Vishukumar Aimanianda, Remi Beau, Mohan S Maddur, Helene Senechal, Pascal Poncet, Jeanpaul LatgeAbstract:Recent reports in mice demonstrate that Basophils function as antigen presenting cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble antigens or IgE-antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating Basophils possess the features of professional APC. We found that unlike dendritic cells (DC) and monocytes, steady-state circulating human Basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed Basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human Basophils to function as professional APC.
-
circulating human Basophils lack the features of professional antigen presenting cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Vishukumar Aimanianda, Remi Beau, Mohan S Maddur, Helene Senechal, Pascal Poncet, Jeanpaul LatgeAbstract:Recent reports in mice demonstrate that Basophils function as antigen presenting cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble antigens or IgE-antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating Basophils possess the features of professional APC. We found that unlike dendritic cells (DC) and monocytes, steady-state circulating human Basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed Basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human Basophils to function as professional APC.
Pascal Poncet - One of the best experts on this subject based on the ideXlab platform.
-
correction corrigendum circulating human Basophils lack the features of professional antigen presenting cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Vishukumar Aimanianda, Remi Beau, Mohan S Maddur, Helene Senechal, Pascal Poncet, Jeanpaul LatgeAbstract:Recent reports in mice demonstrate that Basophils function as antigen presenting cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble antigens or IgE-antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating Basophils possess the features of professional APC. We found that unlike dendritic cells (DC) and monocytes, steady-state circulating human Basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed Basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human Basophils to function as professional APC.
-
circulating human Basophils lack the features of professional antigen presenting cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Vishukumar Aimanianda, Remi Beau, Mohan S Maddur, Helene Senechal, Pascal Poncet, Jeanpaul LatgeAbstract:Recent reports in mice demonstrate that Basophils function as antigen presenting cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble antigens or IgE-antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating Basophils possess the features of professional APC. We found that unlike dendritic cells (DC) and monocytes, steady-state circulating human Basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed Basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human Basophils to function as professional APC.
Helene Senechal - One of the best experts on this subject based on the ideXlab platform.
-
correction corrigendum circulating human Basophils lack the features of professional antigen presenting cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Vishukumar Aimanianda, Remi Beau, Mohan S Maddur, Helene Senechal, Pascal Poncet, Jeanpaul LatgeAbstract:Recent reports in mice demonstrate that Basophils function as antigen presenting cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble antigens or IgE-antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating Basophils possess the features of professional APC. We found that unlike dendritic cells (DC) and monocytes, steady-state circulating human Basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed Basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human Basophils to function as professional APC.
-
circulating human Basophils lack the features of professional antigen presenting cells
Scientific Reports, 2013Co-Authors: Meenu Sharma, Pushpa Hegde, Vishukumar Aimanianda, Remi Beau, Mohan S Maddur, Helene Senechal, Pascal Poncet, Jeanpaul LatgeAbstract:Recent reports in mice demonstrate that Basophils function as antigen presenting cells (APC). They express MHC class II and co-stimulatory molecules CD80 and CD86, capture and present soluble antigens or IgE-antigen complexes and polarize Th2 responses. Therefore, we explored whether human circulating Basophils possess the features of professional APC. We found that unlike dendritic cells (DC) and monocytes, steady-state circulating human Basophils did not express HLA-DR and co-stimulatory molecules CD80 and CD86. Basophils remained negative for these molecules following stimulation with soluble Asp f 1, one of the allergens of Aspergillus fumigatus; Bet v 1, the major birch allergen; TLR2-ligand or even upon IgE cross-linking. Unlike DC, Asp f 1-pulsed Basophils did not promote Th2 responses as analyzed by the secretion of IL-4 in the basophil-CD4+ T cell co-culture. Together, these results demonstrate the inability of circulating human Basophils to function as professional APC.
