NR4A1‐dependent Ly6Clow monocytes contribute to reducing joint inflammation in arthritic mice through Treg cells |
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Authors: | Alexandre Brunet Manon LeBel Benoit Egarnes Carine Paquet‐Bouchard Anne‐Julie Lessard Jacques P. Brown Jean Gosselin |
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Affiliation: | 1. Laboratory of Innate Immunology, Centre de recherche du CHU de Québec—Université Laval, Québec, QC, Canada;2. Division of Rheumatology, CHU de Québec—Université Laval (CHUL), Infectious and Immune Diseases, Centre de recherche du CHU de Québec—Université Laval (CHUL), Québec, QC, Canada;3. Department of Molecular Medicine, Université Laval, Québec, QC, Canada |
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Abstract: | Monocytes are central to the physiopathology of arthritis, but their roles in progression and resolution of the disease remain to be clarified. Using NR4A1?/? mice, which lack patrolling lymphocyte antigen 6C (Ly6Clow) monocytes, we found that inflammatory Ly6Chigh monocytes contribute to rapid development of arthritis in a serum transfer‐induced arthritis (STIA) model. Our experiments suggest that patrolling monocytes do not promote the initiation and progression of arthritis in mice, as severity of symptoms was amplified in NR4A1?/? mice. Moreover, we show that treatment of arthritic wild type (WT) mice with cytosporone B (Csn‐B), a NR4A1‐specific agonist, significantly reduces severity of disease. Effects of Csn‐B were absent in monocyte‐depleted mice treated with clodronate until Ly6Clow monocytes were restored. Adoptive transfer of Ly6Clow monocytes in arthritic NR4A1?/? mice treated with Csn‐B reduces joint inflammation, supporting the regulatory role of Ly6Clow subset on disease development. Our results also reveal that administration of Csn‐B to arthritic mice enhances levels of circulating CD4+CD25+FoxP3+ Treg cells, a process requiring the presence of Ly6Clow monocytes. Together, these data indicate that Ly6Chigh monocytes are involved in the initiation and progression of arthritis and Ly6Clow monocytes contribute to reduce joint inflammation through the mobilization of Treg cells. |
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Keywords: | Arthritis Ly6C Monocytes NR4A1 Regulatory T cells |
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