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A skin colonizer disrupts inflammatory and humoral immune defenses in hidradenitis suppurativa

Agbogan, Viviane A ; Bugault, Florence ; Guenin-Macé, Laure ; Gribonika, Inta LU orcid ; Planchais, Cyril ; Morel, Jean-David ; Delaleu, Jérémie ; Pérez-Chaparro, P Juliana ; Atlan, Michael and Delage, Maïa , et al. (2026) In EMBO Molecular Medicine
Abstract

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a polybacterial dysbiosis devoid of a known pathogen. Here, we report that HS patients mount IgA and IgG responses against skin colonizers, notably Porphyromonas uenonis (Pu), a rare species selectively enriched in severe disease. In these patients, Pu foci are detected in the epidermis, surrounded by IgA deposits, and anti-Pu IgGs cross-react with self-antigens expressed by healthy keratinocytes. Using healthy human skin explants, we demonstrate that patient-derived Pu can cross an intact epidermal barrier, infect and persist within keratinocytes, triggering their expression of pro-inflammatory mediators. In contrast, topical application of Pu on... (More)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a polybacterial dysbiosis devoid of a known pathogen. Here, we report that HS patients mount IgA and IgG responses against skin colonizers, notably Porphyromonas uenonis (Pu), a rare species selectively enriched in severe disease. In these patients, Pu foci are detected in the epidermis, surrounded by IgA deposits, and anti-Pu IgGs cross-react with self-antigens expressed by healthy keratinocytes. Using healthy human skin explants, we demonstrate that patient-derived Pu can cross an intact epidermal barrier, infect and persist within keratinocytes, triggering their expression of pro-inflammatory mediators. In contrast, topical application of Pu on immunocompetent mice elicit cutaneous and systemic humoral immune responses without tissue infection. These findings uncover an impaired innate immune control of Pu in HS patients, linking keratinocyte infection to skin inflammation and humoral autoimmunity. They underscore the potential of targeting cutaneous dysbiosis as a strategy to limit HS progression.

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Contribution to journal
publication status
epub
subject
in
EMBO Molecular Medicine
publisher
Wiley-Blackwell
external identifiers
  • scopus:105033556499
  • pmid:41876796
ISSN
1757-4684
DOI
10.1038/s44321-026-00407-7
language
English
LU publication?
yes
additional info
© 2026. The Author(s).
id
0a915cfb-f394-4ba9-9a0e-eee0f59add27
date added to LUP
2026-03-26 14:44:40
date last changed
2026-05-27 04:01:07
@article{0a915cfb-f394-4ba9-9a0e-eee0f59add27,
  abstract     = {{<p>Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a polybacterial dysbiosis devoid of a known pathogen. Here, we report that HS patients mount IgA and IgG responses against skin colonizers, notably Porphyromonas uenonis (Pu), a rare species selectively enriched in severe disease. In these patients, Pu foci are detected in the epidermis, surrounded by IgA deposits, and anti-Pu IgGs cross-react with self-antigens expressed by healthy keratinocytes. Using healthy human skin explants, we demonstrate that patient-derived Pu can cross an intact epidermal barrier, infect and persist within keratinocytes, triggering their expression of pro-inflammatory mediators. In contrast, topical application of Pu on immunocompetent mice elicit cutaneous and systemic humoral immune responses without tissue infection. These findings uncover an impaired innate immune control of Pu in HS patients, linking keratinocyte infection to skin inflammation and humoral autoimmunity. They underscore the potential of targeting cutaneous dysbiosis as a strategy to limit HS progression.</p>}},
  author       = {{Agbogan, Viviane A and Bugault, Florence and Guenin-Macé, Laure and Gribonika, Inta and Planchais, Cyril and Morel, Jean-David and Delaleu, Jérémie and Pérez-Chaparro, P Juliana and Atlan, Michael and Delage, Maïa and Nassif, Aude and Mouquet, Hugo and Belkaid, Yasmine and Join-Lambert, Olivier and Demangel, Caroline}},
  issn         = {{1757-4684}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{EMBO Molecular Medicine}},
  title        = {{A skin colonizer disrupts inflammatory and humoral immune defenses in hidradenitis suppurativa}},
  url          = {{http://dx.doi.org/10.1038/s44321-026-00407-7}},
  doi          = {{10.1038/s44321-026-00407-7}},
  year         = {{2026}},
}