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| Status |
Public on Sep 10, 2023 |
| Title |
Microenvironmental network of clonal CXCL13+CD4+ T cells and regulatory T cells in pemphigus chronic blisters |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
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 in a specific area, requiring long-term maintenance systemic therapy. 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. 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.
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| Overall design |
Skin with chronic blisters was obtained from patients with pemphigus. Immunologic properties of the skin were analyzed by single-cell RNA and TCR sequencing.
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| Contributor(s) |
Han D, Lee AY, Kim T, Choi JY, Cho MY, Song A, Kim C, Shim JH, Kim HJ, Kim H, D'Angio HB, Preska R, Mayer AT, Kim M, Choi E, Kim T, Shin E, Park K, Kim D, Kim S, Kim JH |
| Citation(s) |
37815865 |
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| Submission date |
Sep 02, 2023 |
| Last update date |
Dec 11, 2023 |
| Contact name |
Taehee Kim |
| E-mail(s) |
[email protected]
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| Organization name |
Gangnam Severance Hospital, Yonsei University College of Medicine
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| Department |
Department of Dermatology and Cutaneous Biology Research Institute
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| Street address |
211 Eonjuro, Gangnam-gu
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| City |
Seoul |
| ZIP/Postal code |
06273 |
| Country |
South Korea |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA1012332 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE242234_RAW.tar |
16.9 Mb |
(http)(custom) |
TAR (of CSV, MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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