European Journal of Immunology
European Journal of Immunology
5 years ago

Interleukin-36 receptor mediates the crosstalk between plasma cells and synovial fibroblasts

Silke Frey, Stefanie Hahne, Dirk Mielenz, Verena Kästele, Verena Schmitt, Olga Wagner, Steffen Gay, Axel J Hueber, Hans-Martin Jäck, Madelaine Hahn, Adriano Taddeo, Andreas Radbruch, Anja Derer, Georg Schett, Wolfgang Schuh, Maximilian Wiendl
The IL-1 family member IL-36α has proinflammatory and pathogenic properties in psoriasis. IL-36α binds to the IL-36 receptor leading to nuclear factor kappa B/mitogen activated protein kinase mediated cytokine release. The IL-36R antagonist prevents recruitment of IL-1 receptor accessory protein and therefore IL-36-dependent cell activation. In inflamed human tissue, we previously could show that resident B cells and plasma cells (PC) express IL-36α. Further, fibroblast-like synoviocytes (FLS) produced proinflammatory cytokines upon IL-36α-stimulation. We hypothesize an IL-36-specific crosstalk between B cells/PCs and FLS permitting a proinflammatory B cell niche. Here, we firstly demonstrated that B cell lines and B cells from healthy donors express IL-36α and stimulation increased IL-36α in B cells and primary plasmablasts/PCs. Moreover, FLS respond specifically to IL-36α by proliferation and production of matrix metalloproteinases via p38/HSP27 signaling. Importantly, IL-36R-deficiency abrogated IL-36α−induced production of inflammatory mediators in FLS and changed the intrinsic FLS-phenotype. Using an in vitro co-culture system, we could show that IL-36R-deficient FLS had a limited capacity to support PC survival compared to wild-type FLS. Hence, we demonstrated an IL-36R-dependent crosstalk between B cells/PCs and FLS. Our data support the concept of initiation and maintenance of a proinflammatory niche by B cells in the joints. This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/eji.201646788

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