Journal Article

Increased Frequency of T Follicular Helper Cells and Elevated Interleukin-27 Plasma Levels in Patients with Pemphigus

Tackenberg, Björn, Seipelt, Maria, Ghoreschi, Kamran, Hertl, Michael, Möbs, Christian, Eming, Rüdiger, Hennerici, Tina, Schmidt, Thomas, Pollmann, Robert

2016

Overview

Pemphigus is an autoimmune disease in which IgG auto-antibodies (auto-ab) against the desmosomal cadherins desmoglein (Dsg) 3 and Dsg1 cause loss of epidermal keratinocyte adhesion. Aim of this study was to investigate cytokines derived from antigen-presenting cells (APC) and their relation to CD4+ T cell subpopulations and to the auto-ab response in pemphigus. In this regard, patients with pemphigus were compared to patients with myasthenia gravis (MG), an unrelated auto-ab-mediated autoimmune disease, and healthy controls. In pemphigus and MG, the plasma concentrations of the APC-derived immunomodulatory cytokine IL-27 were highly increased. Strikingly, IL-27 strongly correlated with Dsg-specific IgG auto-ab titers. T helper (Th) 17 cells were augmented in both pemphigus and MG patients while T follicular helper (Tfh) cells, which are essential in providing B cell help, were increased only in pemphigus along with increasing plasma concentrations of IL-21, a cytokine produced by Th17 and Tfh cells. Moreover, we could detect Dsg3-specific autoreactive T cells producing IL-21 upon ex vivo stimulation with Dsg3. These findings suggest that IL-27 and IL-21-producing T cells, are involved in the pathogenesis of pemphigus. The further characterization of IL-21-producing T cells and of the role of IL-27 will lead to a more defined understanding of the auto-ab response in pemphigus.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Antibodies / Antibody response / Antigen-presenting cells / Antigens / Autoantibodies / Autoantibodies - blood / Autoimmune diseases / Biology and Life Sciences / Case-Control Studies / CD4 antigen / Comparative analysis / Cytokines / Dermatology / Desmoglein 3 / Development and progression / Disease / Disease control / Genetic aspects / Helper cells / Humans / Immunoglobulin G / Immunoglobulin G - blood / Immunology / Immunomodulation / Interleukin / Interleukin 21 / Interleukin 27 / Interleukin-10 - blood / Interleukin-6 - blood / Interleukins / Interleukins - blood / Lupus / Lymphocytes / Lymphocytes B / Lymphocytes T / Medicine and Health Sciences / Myasthenia / Myasthenia gravis / Neuromuscular diseases / Neuromuscular junctions / Pathogenesis / Patients / Pemphigus / Pemphigus - blood / Pemphigus - immunology / Physiological aspects / Plasma levels / Plasmas (physics) / Psoriasis / Receptors, CXCR5 - metabolism / Research and Analysis Methods / Rheumatoid arthritis / Rodents / Skin diseases / Studies / Subpopulations / T cell receptors / T cells / T-Lymphocytes, Helper-Inducer - immunology / T-Lymphocytes, Helper-Inducer - metabolism