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The commensal glycoantigen PSA mitigates inflammation through a novel mechanism of T cell‐T cell interaction (1004.7)
Author(s) -
Jones Mark,
Johnson Jenny,
Cobb Brian
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1004.7
Subject(s) - immune system , immunology , bacteroides fragilis , inflammation , antigen , t cell , biology , secretion , population , medicine , microbiology and biotechnology , endocrinology , environmental health , antibiotics
Asthma and airway inflammatory disease has become the leading cause for ER visits in the US, a four‐decade trend linked to the increasing sterility of western lifestyles and a proposed lack of early microbial antigen exposure. Here, we demonstrate that gastrointestinal contact with the Bacteroides fragilis glycoantigen polysaccharide A (PSA) educates the peripheral immune system to limit the degree of inflammation. Effective immune responses upon re‐exposure to an antigen is typically mediated through antigen‐experienced memory T cells, whereas regulatory T cells are known to play key roles in suppressing immune responses, generally through the secretion of immunosuppressive cytokines like IL‐10. Here, we show that gut exposure to PSA increases a population of antigen experienced CD4 + CD45Rb lo T cells which synergistically amplify IL‐10 production in peripheral tissues upon inflammatory stimulus. We propose a novel pathway of T cell‐crosstalk in which PSA treatment generates commensal glycoantigen experienced T cells in the gut environment that are capable of dampening the magnitude of antigen‐specific memory responses in the periphery. These findings provide a mechanistic framework for the hygiene hypothesis where communication between the microbiota in the gut and the T cell compartment links commensal products to non‐specific peripheral immune quiescence resulting in reduced susceptibility to inflammation. Grant Funding Source : Supported by: NIH DP2 (1‐DP2‐OD‐004225), NIH R01 (5‐R01‐GM082916), AAF (EEA 10‐0187), T32 (AI089474)