» Articles » PMID: 38051587

Single-cell Sequencing Reveals Hippo Signaling As a Driver of Fibrosis in Hidradenitis Suppurativa

Abstract

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by abscesses, nodules, dissecting/draining tunnels, and extensive fibrosis. Here, we integrate single-cell RNA sequencing, spatial transcriptomics, and immunostaining to provide an unprecedented view of the pathogenesis of chronic HS, characterizing the main cellular players and defining their interactions. We found a striking layering of the chronic HS infiltrate and identified the contribution of 2 fibroblast subtypes (SFRP4+ and CXCL13+) in orchestrating this compartmentalized immune response. We further demonstrated the central role of the Hippo pathway in promoting extensive fibrosis in HS and provided preclinical evidence that the profibrotic fibroblast response in HS can be modulated through inhibition of this pathway. These data provide insights into key aspects of HS pathogenesis with broad therapeutic implications.

Citing Articles

Hidradenitis Suppurativa Tunnels: Unveiling a Unique Disease Entity.

Vecin N, Balukoff N, Yaghi M, Gonzalez T, Sawaya A, Strbo N JID Innov. 2025; 5(3):100350.

PMID: 40034103 PMC: 11872476. DOI: 10.1016/j.xjidi.2025.100350.


Integrative systems biology framework discovers common gene regulatory signatures in mechanistically distinct inflammatory skin diseases.

Mishra B, Gou Y, Tan Z, Wang Y, Hu G, Athar M NPJ Syst Biol Appl. 2025; 11(1):21.

PMID: 40016271 PMC: 11868562. DOI: 10.1038/s41540-025-00498-x.


Unveiling Novel Protein Biomarkers for Psoriasis Through Integrated Analysis of Human Plasma Proteomics and Mendelian Randomization.

Mao R, Zhang T, Yang Z, Li J Psoriasis (Auckl). 2024; 14:179-193.

PMID: 39669686 PMC: 11635628. DOI: 10.2147/PTT.S492205.


CD2 expressing innate lymphoid and T cells are critical effectors of immunopathogenesis in hidradenitis suppurativa.

Kashyap M, Mishra B, Sinha R, Jin L, Gou Y, Kumar N Proc Natl Acad Sci U S A. 2024; 121(48):e2409274121.

PMID: 39560648 PMC: 11621750. DOI: 10.1073/pnas.2409274121.


Unveiling new protein biomarkers and therapeutic targets for acne through integrated analysis of human plasma proteomics and genomics.

Deng S, Mao R, He Y Front Immunol. 2024; 15:1452801.

PMID: 39493760 PMC: 11527721. DOI: 10.3389/fimmu.2024.1452801.


References
1.
Della-Torre E, Rigamonti E, Perugino C, Baghai-Sain S, Sun N, Kaneko N . B lymphocytes directly contribute to tissue fibrosis in patients with IgG-related disease. J Allergy Clin Immunol. 2019; 145(3):968-981.e14. PMC: 6960365. DOI: 10.1016/j.jaci.2019.07.004. View

2.
Mehrad B, Keane M, Strieter R . Chemokines as mediators of angiogenesis. Thromb Haemost. 2007; 97(5):755-62. PMC: 3353527. View

3.
Kimball A, Okun M, Williams D, Gottlieb A, Papp K, Zouboulis C . Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa. N Engl J Med. 2016; 375(5):422-34. DOI: 10.1056/NEJMoa1504370. View

4.
Dey A, Varelas X, Guan K . Targeting the Hippo pathway in cancer, fibrosis, wound healing and regenerative medicine. Nat Rev Drug Discov. 2020; 19(7):480-494. PMC: 7880238. DOI: 10.1038/s41573-020-0070-z. View

5.
Lion J, Taflin C, Cross A, Robledo-Sarmiento M, Mariotto E, Savenay A . HLA Class II Antibody Activation of Endothelial Cells Promotes Th17 and Disrupts Regulatory T Lymphocyte Expansion. Am J Transplant. 2015; 16(5):1408-20. DOI: 10.1111/ajt.13644. View