Abstract
Thymic stromal lymphopoietin (TSLP) is produced by epithelial cells and keratinocytes, and is involved in immune homeostasis or inflammation. The mechanism through which TSLP regulates intestinal inflammation is unclear. Here, we report that mouse dendritic cells (DCs) express TSLP both in vitro and in vivo in response to Toll-like receptor ligation in a MyD88-dependent fashion. TSLP is produced by the CD103(+) subset of tolerogenic gut DCs and is downregulated during experimental colitis. TSLP produced by DCs acts directly on T cells by reducing their capacity to produce interleukin (IL)-17 and fostering the development of Foxp3(+) T cells. Consistently, TSLP protects against colitis development through a direct action on T cells, as adoptive transfer of naïve T cells from TSLPR(-/-) to SCID mice results in a more severe colitis, with increased frequency of IL-17-producing T cells and inflammatory cytokines. Hence, we describe a new anti-inflammatory role of TSLP in the gut.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Antigens, CD / metabolism
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Cell Differentiation / genetics
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Cells, Cultured
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Colitis / chemically induced
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Colitis / immunology*
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Cytokines / genetics
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Cytokines / immunology
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Cytokines / metabolism*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Dendritic Cells / pathology
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Dextran Sulfate / administration & dosage
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Disease Progression
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Forkhead Transcription Factors / metabolism
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Integrin alpha Chains / metabolism
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Interleukin-17 / metabolism
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Intestines / immunology
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Intestines / pathology
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Mice
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Mice, Knockout
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Mice, SCID
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Myeloid Differentiation Factor 88 / metabolism
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism*
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T-Lymphocytes, Regulatory / pathology
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Th17 Cells / immunology
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Th17 Cells / metabolism*
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Th17 Cells / pathology
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Thymic Stromal Lymphopoietin
Substances
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Antigens, CD
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Cytokines
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Integrin alpha Chains
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Interleukin-17
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Myeloid Differentiation Factor 88
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alpha E integrins
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Dextran Sulfate
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Thymic Stromal Lymphopoietin
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TSLP protein, mouse