Gut T cell-independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells.

Gut T cell-independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells.
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DOI:
10.1126/sciimmunol.aat7117
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发表时间:
2020-07-31
期刊:
影响因子:
24.8
通讯作者:
Cerutti A
Cerutti A
中科院分区:
医学1区
文献类型:
--
作者:
Grasset EK;Chorny A;Casas-Recasens S;Gutzeit C;Bongers G;Thomsen I;Chen L;He Z;Matthews DB;Oropallo MA;Veeramreddy P;Uzzan M;Mortha A;Carrillo J;Reis BS;Ramanujam M;Sintes J;Magri G;Maglione PJ;Cunningham-Rundles C;Bram RJ;Faith J;Mehandru S;Pabst O;Cerutti A

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肠道通过非冗余T细胞依赖性(TD)和T细胞非依赖性(TI)途径对肠道细菌产生分泌性免疫球蛋白A(SIgA)反应,促进互惠宿主-微生物群相互作用的建立。来自TD途径的SIgA靶向渗透细菌,并且它们的诱导需要T滤泡辅助细胞上的CD 40配体与B细胞上的CD 40的接合。相比之下,来自TI途径的SIgA结合更大范围的细菌,但其产生的机制仍然难以捉摸。在这里,我们表明肠道TI途径需要来自TACI(先天CD 40配体样因子BAFF和APRIL的受体)的CD 40非依赖性B细胞激活信号。TACI诱导的SIgA反应针对一部分肠道微生物群,而不影响其整体组成。值得注意的是,TACI对肠道相关淋巴器官中伊加的TD诱导作用无效。因此,作用于TACI的BAFF/APRIL信号通过肠TI程序编排肠道细菌特异性SIgA应答。
The gut mounts secretory immunoglobulin A (SIgA) responses to commensal bacteria through non-redundant T cell-dependent (TD) and T cell-independent (TI) pathways that promote the establishment of mutualistic host-microbiota interactions. SIgAs from the TD pathway target penetrant bacteria and their induction requires engagement of CD40 on B cells by CD40 ligand on T follicular helper cells. In contrast, SIgAs from the TI pathway bind a larger spectrum of bacteria, but the mechanism underpinning their production remains elusive. Here we show that the intestinal TI pathway required CD40-independent B cell-activating signals from TACI, a receptor for the innate CD40 ligand-like factors BAFF and APRIL. TACI-induced SIgA responses targeted a fraction of the gut microbiota without shaping its overall composition. Of note, TACI was dispensable for TD induction of IgA in gut-associated lymphoid organs. Thus, BAFF/APRIL signals acting on TACI orchestrate commensal bacteria-specific SIgA responses through an intestinal TI program.
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