Murai Masako, Turovskaya Olga, Kim Gisen, Madan Rajat, Karp Christopher L, Cheroutre Hilde, Kronenberg Mitchell
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Nat Immunol. 2009 Nov;10(11):1178-84. doi: 10.1038/ni.1791. Epub 2009 Sep 27.
Regulatory T cells (T(reg) cells) that express the transcription factor Foxp3 suppress the activity of other cells. Here we show that interleukin 10 (IL-10) produced by CD11b(+) myeloid cells in recombination-activating gene 1-deficient (Rag1(-/-)) recipient mice was needed to prevent the colitis induced by transferred CD4(+)CD45RB(hi) T cells. In Il10(-/-)Rag1(-/-) mice, T(reg) cells failed to maintain Foxp3 expression and regulatory activity. The loss of Foxp3 expression occurred only in recipients with colitis, which indicates that the requirement for IL-10 is manifested in the presence of inflammation. IL-10 receptor-deficient (Il10rb(-/-)) T(reg) cells also failed to maintain Foxp3 expression, which suggested that host IL-10 acted directly on the T(reg) cells. Our data indicate that IL-10 released from myeloid cells acts in a paracrine manner on T(reg) cells to maintain Foxp3 expression.
表达转录因子Foxp3的调节性T细胞(Treg细胞)可抑制其他细胞的活性。我们在此表明,重组激活基因1缺陷(Rag1-/-)受体小鼠中CD11b+髓样细胞产生的白细胞介素10(IL-10)对于预防由转移的CD4+CD45RBhi T细胞诱导的结肠炎是必需的。在Il10-/-Rag1-/-小鼠中,Treg细胞无法维持Foxp3表达和调节活性。Foxp3表达的丧失仅发生在患有结肠炎的受体中,这表明对IL-10的需求在炎症存在时表现出来。IL-10受体缺陷(Il10rb-/-)的Treg细胞也无法维持Foxp3表达,这表明宿主IL-10直接作用于Treg细胞。我们的数据表明,髓样细胞释放的IL-10以旁分泌方式作用于Treg细胞以维持Foxp3表达。