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TGFβ promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis

dc.rights.licenseopenen_US
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorLAURENT, Paoline
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorALLARD, Benoit
dc.contributor.authorMANICKI, Pauline
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorJOLIVEL, Valerie
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorLEVIONNOIS, Emeline
dc.contributor.authorJELJELI, Mohamed
dc.contributor.authorHENROT, Pauline
dc.contributor.authorIZOTTE, Julien
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorLELEU, Damien
dc.contributor.authorGROPPI, Alexis
dc.contributor.authorSENESCHAL, Julien
dc.contributor.authorCONSTANS, Joel
dc.contributor.authorCHIZZOLINI, Carlo
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorRICHEZ, Christophe
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorDUFFAU, Pierre
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorLAZARO, Estibaliz
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorFORCADE, Edouard
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorSCHAEVERBEKE, Thierry
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorPRADEU, Thomas
dc.contributor.authorBATTEUX, Frederic
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorBLANCO, Patrick
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorCONTIN-BORDES, Cecile
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorTRUCHETET, Marie Elise
dc.date.accessioned2022-11-15T13:34:34Z
dc.date.available2022-11-15T13:34:34Z
dc.date.issued2021-12
dc.identifier.issn0003-4967 (print) 1468-2060 (online)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/170266
dc.description.abstractEnObjective : Innate lymphoid cells-2 (ILC2) were shown to be involved in the development of lung or hepatic fibrosis. We sought to explore the functional and phenotypic heterogeneity of ILC2 in skin fibrosis within systemic sclerosis (SSc). Methods : Blood samples and skin biopsies from healthy donor or patients with SSc were analysed by immunostaining techniques. The fibrotic role of sorted ILC2 was studied in vitro on dermal fibroblast and further explored by transcriptomic approach. Finally, the efficacy of a new treatment against fibrosis was assessed with a mouse model of SSc. Results : We found that ILC2 numbers were increased in the skin of patients with SSc and correlated with the extent of skin fibrosis. In SSc skin, KLRG1− ILC2 (natural ILC2) were dominating over KLRG1+ ILC2 (inflammatory ILC2). The cytokine transforming growth factor-β (TGFβ), whose activity is increased in SSc, favoured the expansion of KLRG1- ILC2 simultaneously decreasing their production of interleukin 10 (IL10), which regulates negatively collagen production by dermal fibroblasts. TGFβ-stimulated ILC2 also increased myofibroblast differentiation. Thus, human KLRG1- ILC2 had an enhanced profibrotic activity. In a mouse model of SSc, therapeutic intervention-combining pirfenidone with the administration of IL10 was required to reduce the numbers of skin infiltrating ILC2, enhancing their expression of KLRG1 and strongly alleviating skin fibrosis. Conclusion : Our results demonstrate a novel role for natural ILC2 and highlight their inter-relationships with TGFβ and IL10 in the development of skin fibrosis, thereby opening up new therapeutic approaches in SSc.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/*
dc.subject.enFibroblasts
dc.subject.enInflammation
dc.subject.enSystemic sclerosis
dc.title.enTGFβ promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis
dc.typeArticle de revueen_US
dc.identifier.doi10.1136/annrheumdis-2020-219748en_US
dc.subject.halSciences du Vivant [q-bio]/Immunologieen_US
dc.identifier.pubmed34285051en_US
bordeaux.journalAnnals of the rheumatic diseasesen_US
bordeaux.page1594-1603en_US
bordeaux.volume80en_US
bordeaux.hal.laboratoriesImmunoConcEpT - UMR 5164en_US
bordeaux.issue12en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
dc.rights.ccCC BY-NCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Annals%20of%20the%20rheumatic%20diseases&rft.date=2021-12&rft.volume=80&rft.issue=12&rft.spage=1594-1603&rft.epage=1594-1603&rft.eissn=0003-4967%20(print)%201468-2060%20(online)&rft.issn=0003-4967%20(print)%201468-2060%20(online)&rft.au=LAURENT,%20Paoline&ALLARD,%20Benoit&MANICKI,%20Pauline&JOLIVEL,%20Valerie&LEVIONNOIS,%20Emeline&rft.genre=article


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