Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis

By M. Murai, O. Turovskaya, Gisen Kim, R. Madan, C. Karp, Hilde Cheroutre, M. Kronenberg. Nature Immunology, 2009

903 citations recorded by the source corpus.

Regulatory T cells (Treg 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+CD45RBhi T cells. In Il10−/−Rag1−/− mice, Treg 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−/−) Treg cells also failed to maintain Foxp3 expression, which suggested that host IL-10 acted directly on the Treg cells. Our data indicate that IL-10 released from myeloid cells acts in a paracrine manner on Treg cells to maintain Foxp3 expression.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/ae6728c7feb9823ccef6e3a209a0aab1ecb3e38d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

Citations in the corpus

Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. (2012, background): “Our findings refute, however, the notion that exFoxp3 Th cells represent ‘‘exTreg’’ cells, resulting from reprogramming of Treg cells (Bailey-Bucktrout and Bluestone, 2011; Duarte et al., 2009; Murai et al., 2009; Yang et al., 2008; Zhou et al., 2009).”
Intestinal homeostasis and its breakdown in inflammatory bowel disease (2011, background): “Recent evidence suggests that these cells also promote tolerance in part through IL-10 production and maintenance of FOXP3 among colonic T reg cell”
Th17 cells express interleukin-10 receptor and are controlled by Foxp3− and Foxp3+ regulatory CD4+ T cells in an interleukin-10 dependent manner (2011, background): “The in vitro study by Naundorf et al. (2009), who used human PBMCs, suggested that IL-10might directly inhibit TCR-induced IFN-g but not IL-17A production.”
CD19+CD24hiCD38hi B Cells Maintain Regulatory T Cells While Limiting TH1 and TH17 Differentiation (2013, background): “S3B), which has been shown to be important in the maintenance of a functional Treg phenotype (34).”
Coordinated regulation of myeloid cells by tumours (2012, background): “In addition, IL-10 that is produced by macrophages in the inflamed intestinal lamina propria is required to maintain T Reg cell activity and prevent autoimmune coliti”
Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease (2012, background): “In contrast, in studies of a murine colitis model that mimics an inflammatory bowel disease-like syndrome, the Vert-X mouse was used to reveal that myeloid derived cells serves as the predominant source of IL-10 and facilitate the sustenance of Foxp3+ T regulatory cell enrichment in the lamina propr”
Faecalibacterium prausnitzii and human intestinal health. (2013, background): “prausnitzii also induces large amounts of IL-10 in mucosal dendritic cells and macrophages, it may contribute to intestinal homeostasis by inhibiting the production of pro-inflammatory cytokines such as IFN-g, TNF-a, IL6 and IL-12 and enhancing the suppressive activity of Foxp3+ Tregs in the mucosa ”
Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation (2011, positive): “IL-10R Deficiency Does Not Impair Stability of Foxp3 Expression in Treg Cells A recent study suggested that upon adoptive transfer of naive CD4 T cells and Treg cells into lymphopenic hosts, innate immune cell production of IL-10 in the recipients is required to maintain Foxp3 expression (Murai et a”