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

Journal article

Publication Details

Author(s): 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
Journal: European Journal of Immunology
Publication year: 2017
ISSN: 0014-2980


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.

FAU Authors / FAU Editors

Derer, Anja Dr. rer. nat.
Frey, Silke Dr. rer. nat.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Hueber, Axel PD Dr.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Jäck, Hans-Martin Prof. Dr.
Professur für Immunologie
Mielenz, Dirk Prof. Dr.
Medizinische Fakultät
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III
Schmitt, Verena
Professur für Experimentelle Immuntherapie
Schuh, Wolfgang Dr. rer. nat.
Molekular-Immunologische Abteilung in der Medizinischen Klinik 3
Wiendl, Maximilian
Medizinische Klinik 1 - Gastroenterologie, Pneumologie und Endokrinologie

External institutions with authors

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

How to cite

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.

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


Last updated on 2018-21-11 at 06:02