CD98hc regulates the development of experimental colitis by controlling effector and regulatory CD4⁺ T cells

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• 作者：Zaied Ahmed Bhuyan^a ; Hideki Arimochi^a ; Jun Nishida^a ; Keiko Kataoka^a ; Takeshi Kurihara^a ; Chieko Ishifune^a ; Hideki Tsumura^b ; Morihiro Ito^c ; Yasuhiko Ito^c ; Akiko Kitamura^a ; Koji Yasutomo^a ; ^{yasutomo@tokushima-u.ac.jp" class="auth_mail}
• 关键词：CD98 heavy chain ; Colitis ; Regulatory T cells
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：21 February, 2014
• 年：2014
• 卷：444
• 期：4
• 页码：628-633
• 全文大小：952 K

文摘

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^{鈭?/sup> T cells into Rag2鈭?鈭?/sup> 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鈭?/sup> 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.}