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Targeting inducible costimulator expressed on CXCR5 + PD-1 + T H cells suppresses the progression of pemphigus vulgaris

Authors
 A Reum Kim  ;  Dawoon Han  ;  Ji Young Choi  ;  Joon Seok  ;  Song-Ee Kim  ;  Seong-Hoon Seo  ;  Hayato Takahashi  ;  Masayuki Amagai  ;  Su-Hyung Park  ;  Soo-Chan Kim  ;  Eui-Cheol Shin  ;  Jong Hoon Kim 
Citation
 JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol.146(5) : 1070-1079.e8, 2020-11 
Journal Title
 JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 
ISSN
 0091-6749 
Issue Date
2020-11
Keywords
T follicular helper cell ; desmoglein ; humoral immunity ; inducible costimulator ; pemphigus vulgaris
Abstract
Background: Pemphigus vulgaris (PV) is an autoimmune bullous disease mediated by autoantibodies against desmoglein 3 (DSG3). Inducible costimulator (ICOS) is a costimulatory receptor expressed on T cells and influences the activity of T follicular helper (TFH) cells in various autoimmune diseases, but the roles of ICOS and TFH cells in PV remain unclear. Objective: We examined the immunological characteristics, antigen specificity, and pathogenicity of CD4+ T-cell subpopulations, as well as the therapeutic effect of anti-ICOS blocking antibodies in PV. Methods: A mouse model of PV was established by adoptive transfer of immune cells from the skin-draining lymph nodes or spleens of DSG3-expressing skin-grafted Dsg3-/- mice into Rag1-/- mice. The TFH cells and CD4+ T cells in PBMCs from PV patients were examined by flow cytometry. Results: Among CD4+ T cells from the mouse model, ICOS-positive TFH cells were associated with B-cell differentiation and were required for disease induction. Using an MHC class II tetramer, DSG3-specific ICOS+ TFH cells were found to be associated with anti-DSG3 antibody production and expanded in the absence of B cells. In human PV, the frequency of ICOS+CXCR5+PD-1+ memory CD4+ T cells correlated with the autoantibody level. Treatment with anti-ICOS blocking antibodies targeting ICOS+ TFH cells decreased the anti-DSG3 antibody level and delayed disease progression in vivo. Conclusions: Mouse Dsg3-specific ICOS+ TFH cells and human ICOS+CXCR5+PD-1+ TH cells are associated with the anti-DSG3 antibody response in PV. ICOS expressed on CXCR5+PD-1+ TH cells may be a therapeutic target for PV.
Full Text
https://www.sciencedirect.com/science/article/pii/S0091674920304930
DOI
10.1016/j.jaci.2020.03.036
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Soo Chan(김수찬) ORCID logo https://orcid.org/0000-0002-2327-4755
Kim, Jong Hoon(김종훈) ORCID logo https://orcid.org/0000-0002-3385-8180
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180573
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