CD98hc regulates the development of experimental colitis by controlling effector and regulatory CD4 T cells |
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Authors: | Zaied Ahmed Bhuyan Hideki Arimochi Jun Nishida Keiko Kataoka Takeshi Kurihara Chieko Ishifune Hideki Tsumura Morihiro Ito Yasuhiko Ito Akiko Kitamura Koji Yasutomo |
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Institution: | 1. Department of Immunology & Parasitology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan;2. Division of Laboratory Animal Resources, National Research Institute for Child Health and Development, Tokyo, Japan;3. Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi, Japan |
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Abstract: | CD4+ T cell activation is controlled by signaling through the T cell receptor in addition to various co-receptors, and is also affected by their interactions with effector and regulatory T cells in the microenvironment. Inflammatory bowel diseases (IBD) are caused by the persistent activation and expansion of auto-aggressive CD4+ T cells that attack intestinal epithelial cells. However, the molecular basis for the persistent activation of CD4+ T cells in IBD remains unclear. In this study, we investigated how the CD98 heavy chain (CD98hc, Slc3a2) affected the development of colitis in an experimental animal model. Transferring CD98hc-deficient CD4+CD25− T cells into Rag2−/− mice did not cause colitis accompanied by increasing Foxp3+ inducible regulatory T cells. By comparison, CD98hc-deficient naturally occurring regulatory T cells (nTregs) had a decreased capability to suppress colitis induced by CD4+CD25− T cells, although CD98hc-deficient mice did not have a defect in the development of nTregs. Blocking CD98hc with an anti-CD98 blocking antibody prevented the development of colitis. Our results indicate that CD98hc regulates the expansion of autoimmune CD4+ T cells in addition to controlling nTregs functions, which suggests the CD98hc as an important target molecule for establishing strategies for treating colitis. |
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Keywords: | CD98 heavy chain Colitis Regulatory T cells |
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