TGFβ promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis
| Autor: | Edouard Forcade, Pierre Duffau, Estibaliz Lazaro, Emeline Levionnois, Carlo Chizzolini, Benoit Allard, Patrick Blanco, Julien Izotte, Joël Constans, Pauline Henrot, Pauline Manicki, Damien Leleu, Paôline Laurent, Thomas Pradeu, Valérie Jolivel, Alexis Groppi, Christophe Richez, Thierry Schaeverbeke, Julien Seneschal, Mohamed Jeljeli, Marie-Elise Truchetet, Frédéric Batteux, Cécile Contin-Bordes |
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| Přispěvatelé: | Immunology from Concept and Experiments to Translation (ImmunoConcept), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male medicine.medical_treatment Biopsy [SDV]Life Sciences [q-bio] [SHS]Humanities and Social Sciences [SHS.HISPHILSO]Humanities and Social Sciences/History Philosophy and Sociology of Sciences Mice 0302 clinical medicine Fibrosis Transforming Growth Factor beta Immunology and Allergy Medicine Lymphocytes Receptors Immunologic Myofibroblasts Skin integumentary system Anti-Inflammatory Agents Non-Steroidal Cell Differentiation Pirfenidone Middle Aged 3. Good health Interleukin-10 Interleukin 10 Cytokine [SDV.IMM]Life Sciences [q-bio]/Immunology Female Collagen Myofibroblast medicine.drug Adult Pyridones Immunology Systemic Sclerosis General Biochemistry Genetics and Molecular Biology Dermal fibroblast 03 medical and health sciences Rheumatology fibroblasts Animals Humans Lectins C-Type 030203 arthritis & rheumatology Scleroderma Systemic business.industry Gene Expression Profiling medicine.disease Disease Models Animal 030104 developmental biology inflammation Cancer research business Hepatic fibrosis [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Transforming growth factor |
| Zdroj: | Annals of the Rheumatic Diseases Annals of the Rheumatic Diseases, BMJ Publishing Group, 2021, pp.annrheumdis-2020-219748. ⟨10.1136/annrheumdis-2020-219748⟩ |
| ISSN: | 0003-4967 1468-2060 |
| Popis: | ObjectiveInnate 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).MethodsBlood 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.ResultsWe 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.ConclusionOur 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. |
| Databáze: | OpenAIRE |
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