BACKGROUND AND AIMS: Invariant natural killer T [iNKT] cells perform pleiotropic functions in different tissues by secreting a vast array of pro-inflammatory and cytotoxic molecules. However, the presence and function of human intestinal iNKT cells capable of secreting immunomodulatory molecules such as IL-10 has never been reported so far. Here we describe for the first time the presence of IL10-producing iNKT cells [NKT10 cells] in the intestinal lamina propria of healthy individuals and of Crohn's disease [CD] patients. METHODS: Frequency and phenotype of NKT10 cells were analysed ex vivo from intestinal specimens of Crohn's disease [n = 17] and controls [n = 7]. Stable CD-derived intestinal NKT10 cell lines were used to perform in vitro suppression assays and co-cultures with patient-derived mucosa-associated microbiota. Experimental colitis models were performed by adoptive cell transfer of splenic naïve CD4+ T cells in the presence or absence of IL10-sufficient or -deficient iNKT cells. In vivo induction of NKT10 cells was performed by administration of short chain fatty acids [SCFA] by oral gavage. RESULTS: Patient-derived intestinal NKT10 cells demonstrated suppressive capabilities towards pathogenic CD4+ T cells. The presence of increased proportions of mucosal NKT10 cells associated with better clinical outcomes in CD patients. Moreover, an intestinal microbial community enriched in SCFA-producing bacteria sustained the production of IL10 by iNKT cells. Finally, IL10-deficient iNKT cells failed to control the pathogenic activity of adoptively transferred CD4+ T cells in an experimental colitis model. CONCLUSIONS: These results describe an unprecedentd IL10-mediated immunoregulatory role of intestinal iNKT cells in controlling the pathogenic functions of mucosal T helper subsets and in maintaining the intestinal immune homeostasis.

Burrello, C., Strati, F., Lattanzi, G., Diaz-Basabe, A., Mileti, E., Giuffrè, M., et al. (2022). IL10 secretion endows intestinal human iNKT cells with regulatory functions towards pathogenic T lymphocytes. JOURNAL OF CROHN'S AND COLITIS, 16(9), 1461-1474 [10.1093/ecco-jcc/jjac049].

IL10 secretion endows intestinal human iNKT cells with regulatory functions towards pathogenic T lymphocytes

Strati, Francesco
Co-primo
;
Facciotti, Federica
Ultimo
2022

Abstract

BACKGROUND AND AIMS: Invariant natural killer T [iNKT] cells perform pleiotropic functions in different tissues by secreting a vast array of pro-inflammatory and cytotoxic molecules. However, the presence and function of human intestinal iNKT cells capable of secreting immunomodulatory molecules such as IL-10 has never been reported so far. Here we describe for the first time the presence of IL10-producing iNKT cells [NKT10 cells] in the intestinal lamina propria of healthy individuals and of Crohn's disease [CD] patients. METHODS: Frequency and phenotype of NKT10 cells were analysed ex vivo from intestinal specimens of Crohn's disease [n = 17] and controls [n = 7]. Stable CD-derived intestinal NKT10 cell lines were used to perform in vitro suppression assays and co-cultures with patient-derived mucosa-associated microbiota. Experimental colitis models were performed by adoptive cell transfer of splenic naïve CD4+ T cells in the presence or absence of IL10-sufficient or -deficient iNKT cells. In vivo induction of NKT10 cells was performed by administration of short chain fatty acids [SCFA] by oral gavage. RESULTS: Patient-derived intestinal NKT10 cells demonstrated suppressive capabilities towards pathogenic CD4+ T cells. The presence of increased proportions of mucosal NKT10 cells associated with better clinical outcomes in CD patients. Moreover, an intestinal microbial community enriched in SCFA-producing bacteria sustained the production of IL10 by iNKT cells. Finally, IL10-deficient iNKT cells failed to control the pathogenic activity of adoptively transferred CD4+ T cells in an experimental colitis model. CONCLUSIONS: These results describe an unprecedentd IL10-mediated immunoregulatory role of intestinal iNKT cells in controlling the pathogenic functions of mucosal T helper subsets and in maintaining the intestinal immune homeostasis.
Articolo in rivista - Articolo scientifico
Crohn’s disease; IL10; iNKT cells; microbiota; SCFA;
English
1461
1474
14
Burrello, C., Strati, F., Lattanzi, G., Diaz-Basabe, A., Mileti, E., Giuffrè, M., et al. (2022). IL10 secretion endows intestinal human iNKT cells with regulatory functions towards pathogenic T lymphocytes. JOURNAL OF CROHN'S AND COLITIS, 16(9), 1461-1474 [10.1093/ecco-jcc/jjac049].
Burrello, C; Strati, F; Lattanzi, G; Diaz-Basabe, A; Mileti, E; Giuffrè, M; Lopez, G; Cribiù, F; Trombetta, E; Kallikourdis, M; Cremonesi, M; Conforti, F; Botti, F; Porretti, L; Rescigno, M; Vecchi, M; Fantini, M; Caprioli, F; Facciotti, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/364992
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