title: Follicular helper T Cells (Tfh) and IL-21 involvement in the pathogenesis of bullous pemphigoid.
abstract: The pathogenesis of bullous pemphigoid (BP) is characterized by the T cell-dependent production of autoantibodies. Recent studies have indicated that follicular T helper cells (Tfh), the key modulator of B cell activation and autoantibody production, are critical in the development of several autoimmune diseases. Tfh cells perform their functions via IL-21, their hallmark cytokine. In the present study, the frequencies of Tfh cells were investigated in the peripheral blood samples of BP patients to evaluate whether Tfh cells involve in this clinical entity. Significantly higher Tfh cell counts were observed in the peripheral blood of BP patients than those in healthy controls (median: 11.25% vs. 4.95%, respectively; P<0.001). Additionally, the serum IL-21 levels in BP patients were higher than those of the healthy controls (median: 103.98 pg/mL vs 46.77 pg/mL, respectively; P<0.001). The frequencies of Tfh cells and IL-21 levels were both positively correlated with anti-BP180-NC16A autoantibody titers (R = 0.712, P<0.01 and R = 0.578, P = 0.030, respectively). After effective therapy, the frequencies of Tfh cells as well as the serum IL-21 levels in BP patients decreased along with clinical improvement. Most importantly, Tfh depleted CD4(+) T cells and anti-IL-21 neutralization antibody could inhibit the T cell-induced B cell activation and secretion of BP autoantibody in vitro. Those results suggest that Tfh cells play an important role in autoantibody production and are involved in the pathogenesis of BP.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Li
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Liu
authors.forename: Erle
authors.initials: E
authors.lastname: Dang
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.forename: Zheng
authors.initials: Z
authors.lastname: He
authors.forename: Luting
authors.initials: L
authors.lastname: Yang
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Shi
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007378:Interleukins / Q000097:blood*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D024041:Non-Fibrillar Collagens / Q000276:immunology; D010391:Pemphigoid, Bullous / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D054380:Receptors, CXCR5 / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D000097805:Collagen Type XVII; D000098546:Interleukin-21
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015704:CD4 Antigens; D007378:Interleukins; D024041:Non-Fibrillar Collagens; D054380:Receptors, CXCR5; D000097805:Collagen Type XVII; D000098546:Interleukin-21