ABSTRACT
Thymic stromal lymphopoietin (TSLP) is constitutively expressed in the intestine and is known to regulate inflammation in models of colitis. We show that steady-state TSLP expression requires intestinal bacteria and has an important role in limiting the expansion of colonic T helper type 17 (Th17) cells. Inappropriate expansion of the colonic Th17 cells occurred in response to an entirely benign intestinal microbiota, as determined following the colonization of germ-free C57BL/6 or TSLPR(-/-) mice with the altered Schaedler flora (ASF). TSLP-TSLPR (TSLP receptor) interactions also promoted the expansion of colonic Helios(-)Foxp3(+) regulatory T cells, necessary for the control of inappropriate Th17 responses following ASF bacterial colonization. In summary, these data reveal an important role for TSLP-TSLPR signaling in promoting steady-state mutualistic T-cell responses following intestinal bacterial colonization.
Subject(s)
Bacteria/immunology , Colitis/immunology , Cytokines/metabolism , Intestines/immunology , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Animals , Cell Communication , Cell Proliferation , Cells, Cultured , Cytokines/genetics , Cytokines/immunology , Forkhead Transcription Factors/metabolism , Humans , Immunity, Cellular , Immunoglobulins/metabolism , Immunomodulation , Intestines/microbiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Microbiota/immunology , Receptors, Cytokine/metabolism , Thymic Stromal LymphopoietinABSTRACT
The large production of immunoglobulin (Ig)A is energetically costly. The fact that evolution retained this apparent luxury of intestinal class switch recombination to IgA within the human population strongly indicates that there must be a critical specific function of IgA for survival of the species. The function of IgA has been investigated in a series of different models that will be discussed here. While IgA has clear protective functions against toxins or in the context of intestinal viral infections, the function of IgA specific for non-pathogenic commensal bacteria remains unclear. In the context of the current literature we present a hypothesis where secretory IgA integrates as an additional layer of immune function into the continuum of intestinal CD4 T cell responses, to achieve a mutualistic relationship between the intestinal commensal microbiota and the host.
