Oral Escherichia coli colonization factor antigen I fimbriae ameliorate arthritis via IL-35, not IL-27.
Oral Escherichia coli colonization factor antigen I fimbriae ameliorate arthritis via IL-35, not IL-27.
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DOI：
10.4049/jimmunol.1302018
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发表时间：
2014-01-15
期刊：
影响因子：
--
通讯作者：
Pascual DW
中科院分区：
文献类型：
--
作者：
Kochetkova I;Thornburg T;Callis G;Holderness K;Maddaloni M;Pascual DW
沙门氏菌治疗性表达肠毒素大肠杆菌定植因子抗原I(CFA/I)菌毛通过诱导两个调节性T细胞(Treg)亚群：产生转化生长因子β的Foxp3CD39+−+T细胞和产生IL-10的Foxp3+CD39+CD4+T细胞来预防胶原性关节炎。然而，目前尚不清楚CFA/I菌毛是否单独具有保护性，以及是否有其他调节细胞因子参与其中，特别是在EBI3共享的细胞因子、Treg来源的IL-35和APC来源的IL-27的背景下，这两种细胞都能够抑制Th17细胞并调节自身免疫性疾病。随后的评估显示，单次口服纯化的可溶性CFA/I菌毛对CIA的保护作用与沙门氏菌-CFA/I一样有效，并发现Foxp3+CD39+CD4+T细胞是分泌IL-35的来源，而CD11c+细胞产生IL-27受到抑制。为了探讨它们的相关性，CfA/I菌毛处理的IL-27受体缺陷(WSX-1−/−)小鼠与野生型小鼠一样受到CIA的保护，这表明IL-27的作用有限。相比之下，cFA/I菌毛介导的保护作用在EBI3−/−小鼠中减弱，并伴随产生转化生长因子-β和IL-10的Treg的丢失。将B6CD39+CD4+T细胞过继转移到EBI3CFA/I和IL-35同时治疗的−/−小鼠，有效地刺激Tregs抑制促炎CII特异性Th细胞。相反，与B6和EBI3CD39+−/−+T细胞共转移并接受CFA/I加IL-35治疗的受者未能保护小鼠，这暗示了内源性IL-35对CFA/I介导的保护的重要性。因此，CFA/I菌毛可刺激共同诱导转化生长因子-β和IL-10所需的IL-35。
A Salmonella therapeutic expressing enterotoxigenic E. coli colonization factor antigen I (CFA/I) fimbriae protects against collagen-induced arthritis (CIA) by eliciting two regulatory T cell (Treg) subsets: TGF-β-producing Foxp3−CD39+CD4+ and IL-10-producing Foxp3+CD39+CD4+ T cells. However, it is unclear if CFA/I fimbriae alone are protective, and if other regulatory cytokines are involved especially in the context for the EBI3-sharing cytokines, Treg-derived IL-35 and APC-derived IL-27, both capable of suppressing Th17 cells and regulating autoimmune diseases. Subsequent evaluation revealed that a single oral dose of purified, soluble CFA/I fimbriae protected against CIA as effectively as Salmonella-CFA/I, and found Foxp3+CD39+CD4+ T cells as the source of secreted IL-35, whereas IL-27 production by CD11c+ cells was inhibited. Inquiring into their relevance, CFA/I fimbriae-treated IL-27 receptor-deficient (WSX-1−/−) mice were equally protected against CIA as wild-type mice suggesting a limited role for IL-27. In contrast, CFA/I fimbriae-mediated protection was abated in EBI3−/− mice accompanied by the loss of TGF-β- and IL-10-producing Tregs. Adoptive transfer of B6 CD39+CD4+ T cells to EBI3−/− mice with concurrent CFA/I plus IL-35 treatment effectively stimulated Tregs suppressing proinflammatory CII-specific Th cells. Opposingly, recipients co-transferred with B6 and EBI3−/− CD39+CD4+ T cells and treated with CFA/I plus IL-35 failed in protecting mice implicating the importance for endogenous IL-35 to confer CFA/I-mediated protection. Thus, CFA/I fimbriae stimulate IL-35 required for the co-induction of TGF-β and IL-10.
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影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten
影响因子：
--
作者：
Ardissone, Vittoria;Radaelli, Enrico;Traggiai, Elisabetta
通讯作者：
Traggiai, Elisabetta
DOI：
10.1073/pnas.94.22.12041
发表时间：
1997-10-28
影响因子：
11.1
作者：
Devergne, O;Birkenbach, M;Kieff, E
通讯作者：
Kieff, E
影响因子：
4.4
作者：
Diveu, Caroline;McGeachy, Mandy J.;Kastelein, Robert A.
通讯作者：
Kastelein, Robert A.
影响因子：
32.4
作者：
Hamano, S;Himeno, K;Yoshida, H
通讯作者：
Yoshida, H