Functional type 1 regulatory T cells develop regardless of FOXP3 mutations in patients with IPEX syndrome.
Functional type 1 regulatory T cells develop regardless of FOXP3 mutations in patients with IPEX syndrome.
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DOI：
10.1002/eji.201040909
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发表时间：
2011-04
影响因子：
5.4
通讯作者：
Bacchetta, Rosa
中科院分区：
文献类型：
--
作者：
Passerini, Laura;Di Nunzio, Sara;Gregori, Silvia;Gambineri, Eleonora;Cecconi, Massimiliano;Seidel, Markus G.;Cazzola, Giantonio;Perroni, Lucia;Tommasini, Alberto;Vignola, Silvia;Guidi, Luisa;Roncarolo, Maria G.;Bacchetta, Rosa
叉头盒p3 （FOXP3）的突变是自然发生的调节性T细胞（ntreg）的主基因，是ntreg功能受损的原因，导致一种称为免疫失调、多内分泌病、肠病、x连锁（IPEX）综合征的自身免疫性疾病。其他外周耐受机制的相关性，如IPEX综合征患者中1型调节性T （Tr1）细胞（主要的适应性il -10产生Treg亚群）的存在和功能，仍有待澄清。FOXP3突变的Tr1极化细胞从4例IPEX患者的CD4+ T细胞中分化出来，富含IL-10+IL-4 - IFN-γ+ T细胞，这是一种Tr1细胞特异性的细胞因子产生谱，表达低水平的FOXP3和高水平的Granzyme-B。IPEX Tr1细胞具有低增殖性和抑制性，这表明FOXP3突变不会损害其功能。此外，我们从一名FOXP3null患者的外周血中分离出Tr1细胞克隆，证明Tr1细胞在体内存在，并且在没有WT FOXP3的情况下可以在体外扩增。总的来说，我们的结果(i)表明功能性Tr1细胞独立于FOXP3分化，（ii）证实人类Tr1和nTregs是不同的t细胞谱系，（iii）表明在有利的条件下，Tr1细胞可以在IPEX患者中发挥调节功能。
Mutations of forkhead box p3 (FOXP3), the master gene for naturally occurring regulatory T cells (nTregs), are responsible for the impaired function of nTregs, resulting in an autoimmune disease known as the immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. The relevance of other peripheral tolerance mechanisms, such as the presence and function of type 1 regulatory T (Tr1) cells, the major adaptive IL-10-producing Treg subset, in patients with IPEX syndrome remains to be clarified. FOXP3mutated Tr1-polarized cells, differentiated in vitro from CD4+ T cells of four IPEX patients, were enriched in IL-10+IL-4−IFN-γ+ T cells, a cytokine production profile specific for Tr1 cells, and expressed low levels of FOXP3 and high levels of Granzyme-B. IPEX Tr1 cells were hypoproliferative and suppressive, thus indicating that FOXP3 mutations did not impair their function. Furthermore, we isolated Tr1 cell clones from the peripheral blood of one FOXP3null patient, demonstrating that Tr1 cells are present in vivo and they can be expanded in vitro in the absence of WT FOXP3. Overall, our results (i) show that functional Tr1 cells differentiate independently of FOXP3, (ii) confirm that human Tr1 and nTregs are distinct T-cell lineages, and (iii) suggest that under favorable conditions Tr1 cells could exert regulatory functions in IPEX patients.
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DOI：
10.1084/jem.20021139
发表时间：
2002-11-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Levings MK;Sangregorio R;Sartirana C;Moschin AL;Battaglia M;Orban PC;Roncarolo MG
通讯作者：
Roncarolo MG
影响因子：
4.4
作者：
Levings, MK;Sangregorio, R;Roncarolo, MG
通讯作者：
Roncarolo, MG
影响因子：
2.2
作者：
LYONS, AB;PARISH, CR
通讯作者：
PARISH, CR
白介素10在抑制肠炎的调节T细胞功能中的重要作用。
影响因子：
15.3
作者：
Asseman, C;Mauze, S;Leach, M W;Coffman, R L;Powrie, F
通讯作者：
Powrie, F
影响因子：
7.7
作者：
Battaglia, Manuela;Stabilini, Angela;Roncarolo, Maria-Grazia
通讯作者：
Roncarolo, Maria-Grazia