한빛사논문
- 조회595
Dawoon Han1†, A Yeong Lee1†, Taehee Kim1†, Ji Young Choi1, Mi Yeon Cho1, Ahreum Song1, Changhyeon Kim2, Joon Ho Shim3, Hyun Je Kim4, Honesty Kim5, Hillary Blaize D'Angio5, Ryan Preska5, Aaron T. Mayer5, Miri Kim6, Eun-Ji Choi7, Tae-Gyun Kim8, Eui-Cheol Shin9, Kyemyung Park10, Do-Young Kim8*, Soo-Chan Kim11*, and Jong Hoon Kim1*
1Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
2Department of Computer Science and Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
3Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
4Genome Medicine Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
5Enable Medicine, 3499 Edison Way, Menlo Park, CA
6Yeouido St Mary’s Hospital College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
7Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
8Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
9the Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
10Graduate School of Health Science and Technology, College of Information and Biotechnology, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
11Department of Dermatology and Cutaneous Biology Research Institute, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea.
†These authors contributed equally to this work .
*Corresponding authors: Jong Hoon Kim, M.D., Ph.D., Soo-Chan Kim, M.D., Ph.D., Do-Young Kim, M.D., Ph.D.
Abstract
Background: Pemphigus, a rare autoimmune bullous disease mediated by anti-desmoglein autoantibodies, can be controlled with systemic medication like rituximab and high-dose systemic corticosteroids combined with immunosuppressants. However, some patients continue to experience chronically recurrent blisters which require long-term maintenance systemic therapy.
Methods: Skin with chronic blisters was obtained from patients with pemphigus. Immunologic properties of the skin were analyzed by immunofluorescence staining, bulk and single-cell RNA and TCR sequencing, and a highly multiplex imaging technique known as CO-Detection by indEXing (CODEX). Functional analyses were performed by flow cytometry and bulk RNA-sequencing using peripheral blood from healthy donors. Intralesional corticosteroid was injected into patient skin, and changes in chronically recurrent blisters were observed.
Results: We demonstrate the presence of skin tertiary lymphoid structures (TLSs) with desmoglein-specific B cells in chronic blisters from pemphigus patients. In the skin TLSs, CD4+ T cells predominantly produced CXCL13. These clonally expanded CXCL13+CD4+ T cells exhibited features of activated Th1-like cells and downregulated genes associated with T-cell receptor-mediated signaling. Regulatory T cells (Tregs) are in direct contact with CXCL13+CD4+ memory T cells and increased CXCL13 production of CD4+ T cells through IL-2 consumption and TGF-β stimulation. Lastly, Intralesional corticosteroid injection improved chronic blisters and reduce skin TLSs in patients with pemphigus.
Conclusions: This study concludes that skin TLSs are associated with the persistence of chronically recurrent blisters in pemphigus patients, and the microenvironmental network involving CXCL13+CD4+ T cells and Tregs within these structures plays an important role in CXCL13 production.
논문정보
- Research article
- 2023년 10월 (BRIC 등록일 2023-10-11)
- 국내(교신)+국외 연구진
- 의약학 > 면역의학
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