Innate lymphoid cells in skeletal muscle biology and pathology
Inflammatory and dysimmune myopathies (DIM) are classified according to histopathological and immunopathological criteria. In the laboratory, we have identified the myocytic expression of MHC-II as a biomarker characteristic of inclusion myositis (IBM) and anti-synthetase syndromes (ASM) (Aouizerate...
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| Other Authors: | , , , |
| Format: | Doctoral or Postdoctoral Thesis |
| Language: | French |
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HAL CCSD
2022
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| Subjects: | |
| Online Access: | https://theses.hal.science/tel-04191850 https://theses.hal.science/tel-04191850/document https://theses.hal.science/tel-04191850/file/TH2022PA120006.pdf |
| Summary: | Inflammatory and dysimmune myopathies (DIM) are classified according to histopathological and immunopathological criteria. In the laboratory, we have identified the myocytic expression of MHC-II as a biomarker characteristic of inclusion myositis (IBM) and anti-synthetase syndromes (ASM) (Aouizerate 2014; Rigolet, submitted). CD8 + T lymphocytes and NK cells are the main cells producing gamma interferon (IFN gamma) (Aouizerate 2014) which is an activator of macrophages and an inducer of MHC-II. The involvement of NKs in muscular pathology has not been really studied to date, in particular in the myocytic necrosis / regeneration process, whether during DIM or unacquired myopathies such as muscular dystrophies. Our preliminary results indicate that NKs are undetectable in normal muscle of C57 / B1.6 mice. On the other hand, in the muscle of dystrophic mice (Bla/J, deficient in dysferlin; Sgca, deficient in alpha SG), an NK contingent of about 2% of CD45 + is observed. The presence of NK in the muscle of two lines of dystrophic mice suggests that NKs may be involved in the process of myocyte necrosis / regeneration, which is common to both models. Furthermore, NK cells are part of the family of innate lymphoid cells (ILCs), including ILC2s known for their role in the distribution demonstrated in particular in intestinal tissue.The objective of this project is to analyze the role of ILCs in the physiology and biology of normal muscle and in pathological conditions. The ability of NKs to activate macrophages which are themselves necessary for myocyte regeneration and the known role of ILC2s in tissue repair suggest that they may play a key role in the regeneration process. Our work will assess the role of ILCs in 3 different conditions:- Normal post-injury myocyte repair: mouse models of acute muscle injury;- Chronic myocytic necrosis / regeneration: mouse models of muscular dystrophy- NK in human pathology: study on muscle biopsies from patientsThe project has several components:(1) Develop a protocol for the ... |
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