|Title||Dendritic cells produce TSLP that limits the differentiation of Th17 cells, fosters Treg development, and protects against colitis.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Spadoni I, Iliev ID, Rossi G, Rescigno M|
|Date Published||2012 Mar|
|Keywords||Adoptive Transfer, Animals, Antigens, CD, Cell Differentiation, Cells, Cultured, Colitis, Cytokines, Dendritic Cells, Dextran Sulfate, Disease Progression, Forkhead Transcription Factors, Integrin alpha Chains, Interleukin-17, Intestines, Mice, Mice, Knockout, Mice, SCID, Myeloid Differentiation Factor 88, Signal Transduction, T-Lymphocytes, Regulatory, Th17 Cells|
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.
|Alternate Journal||Mucosal Immunol|