TRAF6 is essential for maintenance of regulatory T cells that suppress Th2 type autoimmunity.
TRAF6 is essential for maintenance of regulatory T cells that suppress Th2 type autoimmunity.
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DOI：
10.1371/journal.pone.0074639
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yoshimura A
中科院分区：
文献类型：
--
作者：
Muto G;Kotani H;Kondo T;Morita R;Tsuruta S;Kobayashi T;Luche H;Fehling HJ;Walsh M;Choi Y;Yoshimura A
调节性T细胞（TCRs）通过限制炎症反应来维持免疫稳态。TRAF6通过介导来自包括T细胞受体（TCR）在内的各种受体的信号在先天性和适应性免疫的调节中起关键作用。TRAF6的T细胞特异性缺失已被证明可诱导多器官炎症性疾病，但TRAF6在T细胞中的作用仍有待研究。在这里，我们使用Foxp3-Cre和TRAF6-flox小鼠产生Treg特异性TRAF6缺陷小鼠。Treg特异性TRAF6缺陷（cKO）小鼠发生过敏性皮肤病、关节炎、淋巴结病和高IgE表型。尽管TRAF6-缺陷型Tcl4与野生型Tcl4相比具有相似的体外抑制活性，但TRAF6-缺陷型Tcl4由于Foxp3阳性细胞数量减少而不能非常有效地抑制淋巴细胞减少小鼠中的结肠炎。此外，在没有炎症的雌性cKO小鼠中，TRAF6缺陷型Tcl3的分数与野生型Tcl3相比降低。此外，将Foxp3 + Tcl3过继转移到Rag2-/-小鼠中揭示了TRAF6缺陷型Tcl3在淋巴细胞减少条件下比WT Tcl3更快地转化为Foxp3-细胞。命运定位分析还显示，在TRAF6缺陷型TcB中，TcB从Foxp3+转化为Foxp3-（exFoxp3细胞）加速。这些数据表明，TRAF6在维持Foxp3在TcB和TcB的致病性Th2型转换的抑制中起重要作用。
Regulatory T cells (Tregs) maintain immune homeostasis by limiting inflammatory responses. TRAF6 plays a key role in the regulation of innate and adaptive immunity by mediating signals from various receptors including the T-cell receptor (TCR). T cell-specific deletion of TRAF6 has been shown to induce multiorgan inflammatory disease, but the role of TRAF6 in Tregs remains to be investigated. Here, we generated Treg-specific TRAF6-deficient mice using Foxp3-Cre and TRAF6-flox mice. Treg-specific TRAF6-deficient (cKO) mice developed allergic skin diseases, arthritis, lymphadenopathy and hyper IgE phenotypes. Although TRAF6-deficient Tregs possess similar in vitro suppression activity compared to wild-type Tregs, TRAF6-deficient Tregs did not suppress colitis in lymphopenic mice very efficiently due to reduced number of Foxp3-positive cells. In addition, the fraction of TRAF6-deficient Tregs was reduced compared with wild-type Tregs in female cKO mice without inflammation. Moreover, adoptive transfer of Foxp3 + Tregs into Rag2-/- mice revealed that TRAF6-deficient Tregs converted into Foxp3- cells more rapidly than WT Tregs under lymphopenic conditions. Fate-mapping analysis also revealed that conversion of Tregs from Foxp3+ to Foxp3- (exFoxp3 cells) was accelerated in TRAF6-deficient Tregs. These data indicate that TRAF6 in Tregs plays important roles in the maintenance of Foxp3 in Tregs and in the suppression of pathogenic Th2 type conversion of Tregs.
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影响因子：
20.3
作者：
Cejas, Pedro J.;Walsh, Matthew C.;Choi, Yongwon
通讯作者：
Choi, Yongwon
影响因子：
82.9
作者：
King, Carolyn G.;Kobayashi, Takashi;Choi, Yongwon
通讯作者：
Choi, Yongwon
DOI：
10.1073/pnas.0811556106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Komatsu, Noriko;Mariotti-Ferrandiz, Maria Encarnita;Hori, Shohei
通讯作者：
Hori, Shohei
影响因子：
--
作者：
Namjou, Bahram;Choi, Chan-Bum;Harley, Isaac T. W.;Alarcon-Riquelme, Marta E.;Kelly, Jennifer A.;Glenn, Stuart B.;Ojwang, Joshua O.;Adler, Adam;Kim, Kwangwoo;Gallant, Caroline J.;Boackle, Susan A.;Criswell, Lindsey A.;Kimberly, Robert P.;Brown, Elizabeth E.;Edberg, Jeffrey;Alarcon, Graciela S.;Stevens, Anne M.;Jacob, Chaim O.;Gilkeson, Gary S.;Kamen, Diane L.;Tsao, Betty P.;Anaya, Juan-Manuel;Kim, Eun-Mi;Park, So-Yeon;Sung, Yoon-Kyoung;Guthridge, Joel M.;Merrill, Joan T.;Petri, Michelle;Ramsey-Goldman, Rosalind;Vila, Luis M.;Niewold, Timothy B.;Martin, Javier;Pons-Estel, Bernardo A.;Vyse, Timothy J.;Freedman, Barry I.;Moser, Kathy L.;Gaffney, Patrick M.;Williams, Adrienne H.;Comeau, Mary E.;Reveille, John D.;Kang, Changwon;James, Judith A.;Scofield, R. Hal;Langefeld, Carl D.;Kaufman, Kenneth M.;Harley, John B.;Bae, Sang-Cheol
通讯作者：
Bae, Sang-Cheol
影响因子：
82.9
作者：
Nie, Hong;Zheng, Yingxia;Zhang, Jingwu Z.
通讯作者：
Zhang, Jingwu Z.