IL-10 from marginal zone precursor B cells controls the differentiation of Th17, Tfh and Tfr cells in transplantation tolerance.
IL-10 from marginal zone precursor B cells controls the differentiation of Th17, Tfh and Tfr cells in transplantation tolerance.
复制标题
边缘区前体B细胞的IL-10控制移植耐受性Th17，TFH和TFR细胞的分化。
DOI：
10.1016/j.imlet.2016.01.002
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发表时间：
2016-02
影响因子：
4.4
通讯作者：
Bromberg JS
中科院分区：
文献类型：
--
作者：
Lal G;Kulkarni N;Nakayama Y;Singh AK;Sethi A;Burrell BE;Brinkman CC;Iwami D;Zhang T;Hehlgans T;Bromberg JS
已知B细胞控制次级淋巴组织中CD4T细胞的分化。我们假设，在耐受过程中，边缘带前体(MZP)调节性B细胞表达IL-10控制效应T细胞和调节性T细胞的分化和定位。用供体特异性输血(DST)和抗CD40L单抗共刺激阻断C57BL/6小鼠对同种异体心脏移植的耐受。B细胞耗尽或IL-10缺乏阻碍了耐受性，导致B细胞区和T细胞区的滤泡调节性CD4+T细胞(TFR)减少，T滤泡辅助细胞(TFH)IL-21表达增加。IL-21与IL-6共同诱导CCR6+Th17，引起排斥反应。IL-6、IL-21、IL-21R或CCR6的缺乏或阻断可预防B细胞耗竭诱导的急性细胞排斥反应，而激动型mCCL20-Ig则可诱导排斥反应。在耐受原处理的CD19Cre+/−：：IL-10fl/fl小鼠中过继转移IL-10+/+MZP，挽救了Tfh和Tfr细胞在B细胞滤泡中的定位，防止了同种异体移植排斥反应。MZP B细胞IL-10是耐受所必需的，控制Th17、Tfh和Tfr细胞在次级淋巴组织中的分化和位置。这对于理解耐受诱导和B细胞耗竭如何防止耐受有一定的意义。
B cells are known to control CD4 T 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.