Abstract
BackgroundWe recently demonstrated that BATF, a member of the activator protein-1 (AP-1) family, regulates osteoarthritic cartilage destruction. Here, we explored the roles and regulatory mechanisms of BATF in collagen-induced arthritis (CIA) in mice.MethodsCIA and K/BxN serum transfer were used to generate inflammatory arthritis models in wild-type (WT) and Batf−/− mice. RA manifestations were determined by examining CIA incidence, clinical score, synovitis, synovial hyperplasia, angiogenesis in inflamed synovium, pannus formation, bone erosion, and cartilage destruction. Immune features in RA were analyzed by examining immune cell populations and cytokine production.ResultsBATF was upregulated in the synovial tissues of joints in which inflammatory arthritis had been caused by CIA or K/BxN serum transfer. The increases in CIA incidence, clinical score, and autoantibody production in CIA-induced WT mice were completely abrogated in the corresponding Batf−/− DBA/1 J mice. Genetic ablation of Batf also inhibited CIA-induced synovitis, synovial hyperplasia, angiogenesis in synovial tissues, pannus formation, bone erosion, and cartilage destruction. Batf knockout inhibited the differentiation of T helper (Th)17 cells and the conversion of CD4+Foxp3+ cells to CD4+IL-17+ cells. However, BATF did not modulate the functions of fibroblast-like synoviocytes (FLS), including the expressions of chemokines, matrix-degrading enzymes, vascular endothelial growth factor, and receptor activator of NF-κB ligand (RANKL).ConclusionOur findings indicate that BATF crucially mediates CIA by regulating Th cell differentiation without directly affecting the functions of FLS.
Highlights
We recently demonstrated that Basic leucine zipper transcription factor (BATF), a member of the activator protein-1 (AP-1) family, regulates osteoarthritic cartilage destruction
We examined whether BATF is required for collagen-induced arthritis (CIA), which is a commonly used experimental model of inflammatory arthritis caused by a T cell-dependent, antibody-mediated autoimmune response directed against cartilage type II collagen [19]
We reveal that BATF regulates collageninduced arthritis (CIA) by regulating T helper (Th) cell differentiation without directly affecting the functions of fibroblast-like synoviocytes (FLS)
Summary
We recently demonstrated that BATF, a member of the activator protein-1 (AP-1) family, regulates osteoarthritic cartilage destruction. BATF (basic leucine zipper transcription factor, ATF-like) is a member of the activator protein-1 (AP-1) family whose members regulate various biological functions [1,2,3]. We recently demonstrated that BATF regulates osteoarthritis (OA) in mice by modulating anabolic and catabolic gene expression in chondrocytes [4]. OA and rheumatoid arthritis (RA), which are the most common types of joint arthritis, share certain phenotypic features, such as cartilage destruction [5]. These diseases clearly differ in their etiologies, pathogenic mechanisms, and the cell types associated with each pathogenesis. RA is an inflammatory autoimmune disease that mainly targets
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