title: Dendritic cells produce TSLP that limits the differentiation of Th17 cells, fosters Treg development, and protects against colitis.
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.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Spadoni
authors.forename: I D
authors.initials: ID
authors.lastname: Iliev
authors.forename: G
authors.initials: G
authors.lastname: Rossi
authors.forename: M
authors.initials: M
authors.lastname: Rescigno
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate / Q000008:administration & dosage; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000378:metabolism; D039001:Integrin alpha Chains / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D039001:Integrin alpha Chains; D020381:Interleukin-17; D053594:Myeloid Differentiation Factor 88; C091367:alpha E integrins; D016264:Dextran Sulfate; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse