کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3355258 1591556 2016 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
IL-10 from marginal zone precursor B cells controls the differentiation of Th17, Tfh and Tfr cells in transplantation tolerance
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
IL-10 from marginal zone precursor B cells controls the differentiation of Th17, Tfh and Tfr cells in transplantation tolerance
چکیده انگلیسی


• Depletion of B cells prevents co-stimulatory blockade induced transplantation tolerance.
• Depletion of B cells or deficiency of IL-10 in B cell induces Th17 cells in spleen and lymph nodes.
• Deficiency of IL-10 in B cells altered the location of follicular regulatory CD4T cell (Tfr) and follicular helper CD4T cell (Tfh) in secondary lymphoid organs.
• Neutralization of IL-6, IL-21 or deficiency of CCR6 prevents B cell depletion induced cardiac allograft rejection in tolerogen treated mice.

B cells are known to control CD4T cell differentiation in secondary lymphoid tissues. We hypothesized that IL-10 expression by marginal zone precursor (MZP) regulatory B cells controls the differentiation and positioning of effector and regulatory T cells during tolerization. Costimulatory blockade with donor-specific transfusion (DST) and anti-CD40L mAb in C57BL/6 mice induced tolerance to allogeneic cardiac allograft. B cell depletion or IL-10 deficiency in B cells prevented tolerance, resulting in decreased follicular regulatory CD4+ T cells (Tfr) and increased IL-21 expression by T follicular helper (Tfh) cells in the B cell and T cell zones. IL-21 acted with IL-6 to induce CCR6+ Th17 that caused rejection. Deficiency or blockade of IL-6, IL-21, IL-21R, or CCR6 prevented B cell depletion-induced acute cellular rejection; while agonistic mCCL20-Ig induced rejection. Adoptive transfer of IL-10+/+ MZP in tolerogen treated CD19-Cre+/−:IL-10fl/fl mice rescued the localization of Tfh and Tfr cells in the B cell follicle and prevented allograft rejection. MZP B cell IL-10 is necessary for tolerance and controls the differentiation and position of Th17, Tfh and Tfr cells in secondary lymphoid tissues. This has implications for understanding tolerance induction and how B cell depletion may prevent tolerance.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Immunology Letters - Volume 170, February 2016, Pages 52–63
نویسندگان
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