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Publication : T<sub>reg</sub> cells limit IFN-γ production to control macrophage accrual and phenotype during skeletal muscle regeneration.

First Author  Panduro M Year  2018
Journal  Proc Natl Acad Sci U S A Volume  115
Issue  11 Pages  E2585-E2593
PubMed ID  29476012 Mgi Jnum  J:259771
Mgi Id  MGI:6144192 Doi  10.1073/pnas.1800618115
Citation  Panduro M, et al. (2018) Treg cells limit IFN-gamma production to control macrophage accrual and phenotype during skeletal muscle regeneration. Proc Natl Acad Sci U S A 115(11):E2585-E2593
abstractText  Skeletal muscle regeneration is a highly orchestrated process that depends on multiple immune-system cell types, notably macrophages (MFs) and Foxp3(+)CD4(+) regulatory T (Treg) cells. This study addressed how Treg cells rein in MFs during regeneration of murine muscle after acute injury with cardiotoxin. We first delineated and characterized two subsets of MFs according to their expression of major histocompatibility complex class II (MHCII) molecules, i.e., their ability to present antigens. Then, we assessed the impact of Treg cells on these MF subsets by punctually depleting Foxp3(+) cells during the regenerative process. Treg cells controlled both the accumulation and phenotype of the two types of MFs. Their absence after injury promoted IFN-gamma production, primarily by NK and effector T cells, which ultimately resulted in MF dysregulation and increased inflammation and fibrosis, pointing to compromised muscle repair. Thus, we uncovered an IFN-gamma-centered regulatory layer by which Treg cells keep MFs in check and dampen inflammation during regeneration of skeletal muscle.
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