Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells

By Esen Sefik, N. Geva-Zatorsky, Sungwhan F. Oh, L. Konnikova, D. Zemmour, A. McGuire, Dalia Burzyn, A. Ortíz-López, M. Lobera, Jianfei Yang and 7 more. Science, 2015

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Gut microbes make T cells keep the peace Our guts harbor trillions of microbial inhabitants, some of which regulate the types of immune cells that are present in the gut. For instance, Clostridium species of bacteria induce a type of T cell that promotes tolerance between the host and its microbial contents. Ohnmacht et al. and Sefik et al. characterized a population of gut regulatory T cells in mice, which required gut microbiota to survive. Multiple bacterial species of the microbiota could induce transcription factor–expressing regulatory T cells that helped maintain immune homeostasis. Mice engineered to lack these transcription factors exhibited enhanced susceptibility to colonic inflammation and had elevated amounts of proinflammatory molecules associated with allergies (see the Perspective by Hegazy and Powrie). Science, this issue pp. 989 and 993 Microbes resident in the gut induce an immunoregulatory population of T cells that promote immune homeostasis. [Also see Perspective by Hegazy and Powrie] T regulatory cells that express the transcription factor Foxp3 (Foxp3+ Tregs) promote tissue homeostasis in several settings. We now report that symbiotic members of the human gut microbiota induce a distinct Treg population in the mouse colon, which constrains immuno-inflammatory responses. This induction—which we find to map to a broad, but specific, array of individual bacterial species—requires the transcription factor Rorγ, paradoxically, in that Rorγ is thought to antagonize FoxP3 and to promote T helper 17 (TH17) cell differentiation. Rorγ’s transcriptional footprint differs in colonic Tregs and TH17 cells and controls important effector molecules. Rorγ, and the Tregs that express it, contribute substantially to regulating colonic TH1/TH17 inflammation. Thus, the marked context-specificity of Rorγ results in very different outcomes even in closely related cell types.

Subfields: Immunology, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3b2645fcc43c842bf70556797b79c1a962055450

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Citations in the corpus

Holobionts as Units of Selection and a Model of Their Population Dynamics and Evolution (2018, background): “2011), and the subsequent induction of regulatory T lymphocytes (Sefik et al. 2015), and immunoglobulin A synthesis (Peterson et al.”
Regulatory T Cells and Human Disease. (2020, background): “In contrast, RORγt+Helios− Tregs are pTregs induced by the presence of intestinal microbiota, and the loss of RORγt expression by Tregs results in severe intestinal inflammation (86, 87).”
The gut microbiome: Relationships with disease and opportunities for therapy (2018, background): “Clostridium species, including those belonging to clusters IV, XIVa, and XVI II, induce CD4+Foxp3+ T reg cells, via production of SCFAs (Atarashi et al., 2013; Sefik et al., 2015; Geva-Zatorsky et al., 2017).”
Mining the human gut microbiota for immunomodulatory organisms (2017, positive): “Data on RORg+Helios Tregs and Th17 cells argue that at least some of the observed activities can be recapitulated in SPF mice (Sefik et al., 2015; Tan et al., 2016).”
Homeostatic immunity and the microbiota (2017, neutral): “Notably, peripherally-induced Treg cells are reduced under germ free conditions (Geuking et al., 2011; Ohnmacht et al., 2015; Sefik et al., 2015; Yang et al., 2016).”