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 naive 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.

Dendritic cells produce TSLP that limits the differentiation of Th17 cells, fosters Treg development, and protects against colitis / I. Spadoni, I. Iliev, G. Rossi, M. Rescigno. - In: MUCOSAL IMMUNOLOGY. - ISSN 1933-0219. - 5:2(2012 Mar), pp. 184-193.

Dendritic cells produce TSLP that limits the differentiation of Th17 cells, fosters Treg development, and protects against colitis

M. Rescigno
2012

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 naive 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.
thymic stromal lymphopoietin; intestinal immune homeostasis; airway epithelial-cells; CD4(+) T-cells; retinoic-acid; inflammation; expression; beta; macrophages; disease
Settore BIO/13 - Biologia Applicata
mar-2012
Article (author)
File in questo prodotto:
File Dimensione Formato  
mi201164a.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 463.28 kB
Formato Adobe PDF
463.28 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/297111
Citazioni
  • ???jsp.display-item.citation.pmc??? 48
  • Scopus 85
  • ???jsp.display-item.citation.isi??? 84
social impact