Intestinal Bacterial Colonization Induces Mutualistic Regulatory T Cell Responses

Markus B. Geuking, et al. 2011. Immunity 34, 794-806

Speaker: Shih-Ying Wu (吳思瑩)                                 Time: 13:00~14:00, Oct. 05, 2011

Commentator: Dr. Lien-I Hor (何漣漪老師)                Place: Room 601

Abstract:

There are many mutualistic microbiota located on gut of human. It’s believed that these bacteria and hosts’ immune system are mutually influenced. Some papers pointed out that some bacteria or bacterial components could induce CD4⁺ T cell response, including T helper 1 (Th1), Th17, and Foxp3⁺ regulatory (Treg) cells, in which the induced CD4⁺ T cell would regulate immune homeostasis with an unknown mechanism. To address this question, the authors colonized germ-free mice with altered Schaedler flora (ASF). They found that the Treg cell population was expansion in the column lamina propria (cLP), regardless of genome background of mice. Besides, the expression of CD103 was increased in cLP. The CD103⁺ effector Treg cells were considered to be able to inhibit immune response previously. Importantly, the expression of regulatory cytokine,interleukine 10 (IL-10), was elevated after ASF colonization. The intestinal CD4⁺ T cells would diverse to Th1 and Th17 with a blockade of IL-10 signal. Thus, IL-10 is an essential cytokine for intestinal immune homeostasis. To make sure that the CD4⁺ T cell homeostasis was really due to a Tregdefect, rather than an intrinsic differentiation of Th1 and Th17, the authors transferred wild type Treg cells into SMARTA germ-free mice. They found that the induced Treg (iTreg) cells would prevent immune deviation of intestinal immune system. Then the authors wanted to find out how colonization of the activated Treg cells. They observed how ASF colonized in Myd88^-/- Ticam1^-/- mice, which are deficient for TLR signaling. Upon colonization, the generation of Foxp3⁺Treg cells and CD103⁺ effector Treg cells was abrogated, suggesting that the TLR signaling was required for the activation of the Treg cells. Because colonization would cause epithelial damage, they used 2% dextran sulfate sodium (DSS) to destroy the colonic epithelial of mice. They found that the Treg cells, but not Th17 and Th1 cells, would be activated. In summary, ASF colonization could damage the hosts’ colonic epithelial, and activate Treg cells through TLR signaling transduction. In addition, Treg cell responses were necessary for Th1 and Th17 cell homeostasis.

References:

1. Barness, M.J. et al. Regulatory T cells reinforce intestinal homeostasis. Immunity 31, 401-411 (2009).