title: Increased Frequency of T Follicular Helper Cells and Elevated Interleukin-27 Plasma Levels in Patients with Pemphigus.
abstract: 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.
authors.affiliation: Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Hennerici
authors.affiliation: Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Pollmann
authors.affiliation: Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmidt
authors.affiliation: Department of Neurology, Philipps University Marburg, Marburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Seipelt
authors.affiliation: Department of Neurology, Philipps University Marburg, Marburg, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Tackenberg
authors.affiliation: Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Möbs
authors.affiliation: Department of Dermatology, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Kamran
authors.initials: K
authors.lastname: Ghoreschi
authors.affiliation: Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hertl
authors.affiliation: Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Eming
mesh_terms: D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000097:blood*; D010392:Pemphigus / Q000097:blood* / Q000276:immunology; D054380:Receptors, CXCR5 / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D001323:Autoantibodies; C095085:CXCR5 protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D007074:Immunoglobulin G; D015850:Interleukin-6; D007378:Interleukins; C464565:MYDGF protein, human; D054380:Receptors, CXCR5; D016753:Interleukin-10; D000098546:Interleukin-21