دورية أكاديمية
IL10 secretion endows intestinal human iNKT cells with regulatory functions towards pathogenic T lymphocytes
| العنوان: | IL10 secretion endows intestinal human iNKT cells with regulatory functions towards pathogenic T lymphocytes |
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| المؤلفون: | Burrello, Claudia, Strati, Francesco, Lattanzi, Georgia, Diaz-Basabe, Angelica, Mileti, Erika, Giuffrè, Maria Rita, Lopez, Gianluca, Cribiù, Fulvia Milena, Trombetta, Elena, Kallikourdis, Marinos, Cremonesi, Marco, Conforti, Francesco, Botti, Fiorenzo, Porretti, Laura, Rescigno, Maria, Vecchi, Maurizio, Fantini, Massimo C, Caprioli, Flavio, Facciotti, Federica |
| المساهمون: | C. Burrello, F. Strati, G. Lattanzi, A. Diaz-Basabe, E. Mileti, M.R. Giuffrè, G. Lopez, F.M. Cribiù, E. Trombetta, M. Kallikourdi, M. Cremonesi, F. Conforti, F. Botti, L. Porretti, M. Rescigno, M. Vecchi, M.C. Fantini, F. Caprioli, F. Facciotti |
| بيانات النشر: | Oxford Academic |
| سنة النشر: | 2022 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Crohn’s disease, IL10, iNKT cell, microbiota, SCFA, Settore MED/04 - Patologia Generale, Settore MED/12 - Gastroenterologia |
| الوصف: | 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 to secrete 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 analyzed 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 cocultures with patients'-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 SCFA by oral gavage. Results: Patient's 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 cell failed to control the pathogenic activity of adoptively transferred CD4+ T cells in an experimental colitis model. Conclusions: These results describe an unprecedent 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35358301; info:eu-repo/semantics/altIdentifier/wos/WOS:000791183100001; volume:16; issue:9; firstpage:1461; lastpage:1474; numberofpages:14; journal:JOURNAL OF CROHN'S AND COLITIS; https://hdl.handle.net/2434/921822Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85134474782 |
| DOI: | 10.1093/ecco-jcc/jjac049 |
| الإتاحة: | https://doi.org/10.1093/ecco-jcc/jjac049Test https://hdl.handle.net/2434/921822Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.22EA92A7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/ecco-jcc/jjac049 |
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