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

Schmitt V, Hahn M, Kästele V, Wagner O, Wiendl M, Derer A, Taddeo A, Hahne S, Radbruch A, Jäck HM, Schuh W, Mielenz D, Gay S, Schett G, Hueber A, Frey S (2017)

Publication Type: Journal article

Publication year: 2017

Journal

European Journal of Immunology Wiley-VCH Verlag

DOI: 10.1002/eji.201646788

Abstract

The IL-1 family member IL-36? has proinflammatory and pathogenic properties in psoriasis. IL-36? 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-36?. Further, fibroblast-like synoviocytes (FLS) produced proinflammatory cytokines upon IL-36?-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-36? and stimulation increased IL-36? in B cells and primary plasmablasts/PCs. Moreover, FLS respond specifically to IL-36? by proliferation and production of matrix metalloproteinases via p38/HSP27 signaling. Importantly, IL-36R-deficiency abrogated IL-36?-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.

Authors with CRIS profile

Verena Schmitt Professur für Experimentelle Immuntherapie Maximilian Wiendl Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Anja Derer Department of Radiation Oncology Hans-Martin Jäck Professur für Immunologie Wolfgang Schuh Department of Molecular Immunology Dirk Mielenz Medizinische Fakultät Georg Schett Lehrstuhl für Innere Medizin III Axel Hueber Department of Medicine 3 – Rheumatology and Immunology Silke Frey Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Deutsches Rheuma-Forschungszentrum (DRFZ) DE Germany (DE) Carol Davila University of Medicine and Pharmacy / Universitatea de Medicină și Farmacie „Carol Davila” (UMF București) RO Romania (RO)

How to cite

APA:

Schmitt, V., Hahn, M., Kästele, V., Wagner, O., Wiendl, M., Derer, A.,... Frey, S. (2017). Interleukin-36 receptor mediates the crosstalk between plasma cells and synovial fibroblasts. European Journal of Immunology. https://dx.doi.org/10.1002/eji.201646788

MLA:

Schmitt, Verena, et al. "Interleukin-36 receptor mediates the crosstalk between plasma cells and synovial fibroblasts." European Journal of Immunology (2017).

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