Nonclassical Ly6C− Monocytes Drive the Development of Inflammatory Arthritis in Mice

Autor: Alexander V. Misharin, Carla M. Cuda, Rana Saber, Jason D. Turner, Angelica K. Gierut, G. Kenneth Haines III, Sergejs Berdnikovs, Andrew Filer, Andrew R. Clark, Christopher D. Buckley, Gökhan M. Mutlu, G.R. Scott Budinger, Harris Perlman
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Cell Reports, Vol 9, Iss 2, Pp 591-604 (2014)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2014.09.032
Popis: Different subsets and/or polarized phenotypes of monocytes and macrophages may play distinct roles during the development and resolution of inflammation. Here, we demonstrate in a murine model of rheumatoid arthritis that nonclassical Ly6C− monocytes are required for the initiation and progression of sterile joint inflammation. Moreover, nonclassical Ly6C− monocytes differentiate into inflammatory macrophages (M1), which drive disease pathogenesis and display plasticity during the resolution phase. During the development of arthritis, these cells polarize toward an alternatively activated phenotype (M2), promoting the resolution of joint inflammation. The influx of Ly6C− monocytes and their subsequent classical and then alternative activation occurs without changes in synovial tissue-resident macrophages, which express markers of M2 polarization throughout the course of the arthritis and attenuate joint inflammation during the initiation phase. These data suggest that circulating Ly6C− monocytes recruited to the joint upon injury orchestrate the development and resolution of autoimmune joint inflammation.
Databáze: Directory of Open Access Journals