在多數(shù)免疫和炎癥環(huán)境下,，淋巴內(nèi)穩(wěn)態(tài)是由各種各樣的調(diào)節(jié)性T細(xì)胞和轉(zhuǎn)錄因子FoxP3與特異的轉(zhuǎn)錄輔因子的相互作用來共同維持,。
5月10日，Cell在線發(fā)表了哈佛醫(yī)學(xué)院和凱特林癌癥中心合作的一篇題為《An N-Terminal Mutation of the F oxp3 Transcription Factor Alleviates Arthritis but Exacerbates Diabetes》研究文章,，發(fā)現(xiàn)轉(zhuǎn)錄因子FoxP3 N末端的一個突變可以減緩關(guān)節(jié)炎,，反而卻加劇糖尿病,。
研究報道了FoxP3的一個普通插入突變（GFP-Foxp3）改變了分子相互作用：阻止了與HIF- 1a卻提高了與IRF4的相互作用。這些調(diào)節(jié)性T細(xì)胞的側(cè)面發(fā)生輕微地改變,，導(dǎo)致過分地呈現(xiàn)依賴IRF4的轉(zhuǎn)錄子活性,。GFP- FoxP3小鼠在保持調(diào)節(jié)性T細(xì)胞依賴IRF4的功能優(yōu)先地抑制T細(xì)胞幫助B細(xì)胞、Th2和Th17等細(xì)胞類型的分化的同時,，卻對自身免疫病表現(xiàn)出相異的敏感性：在K/BxN模型中對抗體介導(dǎo)的關(guān)節(jié)炎起防護(hù)作用,，而在NOD背景的小鼠中對糖尿病表現(xiàn)出更高的易感性。
FoxP3分子的相互作用可以影響調(diào)節(jié)性T細(xì)胞的特異子功能和它們調(diào)節(jié)的免疫疾病,，最終導(dǎo)致相異的免疫調(diào)節(jié),。(生物谷 Bioon.com)
doi.org/10.1016/j.immuni.2012.04.007
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PMID:
An N-Terminal Mutation of the Foxp3 Transcription Factor Alleviates Arthritis but Exacerbates Diabetes
Jaime Darce1,Dipayan Rudra2,Li Li1,Junko Nishio1,Daniela Cipolletta1,Alexander Y. Rudensky2,Diane Mathis1,Christophe Benoist1
1 Division of Immunology， Department of Microbiology and Immunobiology,， Harvard Medical School,， Boston， MA 02115,， USA
2 Howard Hughes Medical Institute and Immunology Program， Memorial Sloan-Kettering Cancer Center,， New York,， NY 10065， USA
Received 19 July 2011. Revised 12 January 2012. Accepted 4 April 2012. Available online 10 May 2012. Published online： May 10,， 2012.
Summary
Maintenance of lymphoid homeostasis in a number of immunological and inflammatory contexts is served by a variety of regulatory T (Treg) cell subtypes and depends on interaction of the transcription factor FoxP3 with specific transcriptional cofactors. We report that a commonly used insertional mutant of FoxP3 (GFP-Foxp3) modified its molecular interactions,， blocking HIF-1α but increasing IRF4 interactions. The transcriptional profile of these Treg cells was subtly altered， with an overrepresentation of IRF4-dependent transcripts. In keeping with IRF4-dependent function of Treg cells to preferentially suppress T cell help to B cells and Th2 and Th17 cell-type differentiation,， GFP-FoxP3 mice showed a divergent susceptibility to autoimmune disease： protection against antibody-mediated arthritis in the K/BxN model,， but greater susceptibility to diabetes on the NOD background. Thus， specific subfunctions of Treg cells and the immune diseases they regulate can be influenced by FoxP3's molecular interactions,， which result in divergent immunoregulation.
