Assistant Professor University of Miami Miller School of Medicine Miami, Florida, United States
Disclosure(s):
Natasa Strbo, MD PhD: No financial relationships to disclose
Introduction/Rationale: Skin-resident gamma delta (GD) T cells provide rapid innate immune protection and are shaped by interactions with the cutaneous microbiota. Hidradenitis suppurativa (HS) is a chronic, painful inflammatory skin disease marked by nodules and tunnels that disproportionately affects women . Although microbial dysbiosis is implicated in HS, the contribution of specific bacteria to disease initiation remains unclear. Recent preliminary analyses identified enrichment of Actinotignum species in HS tunnels, coinciding with early accumulation of IL-17-producing GDT cells and neutrophils.
Methods: A patient-derived Gram+ facultative anaerobe, Actinotignum schaalii (A. schaalii) strain or the commensal Staphylococcus epidermidis was injected subcutaneously into murine axillary skin (C57BL/6-H2BEGFP mice). Lesional (abscess-forming) tissue was collected at 24 and 72 hours and analyzed by histology, bulk RNA sequencing, and spectral flow cytometry. Cytokine expression (IL-17, IL-1β, TNF-α) was assessed by qPCR. Murine findings were compared with early human HS lesions.
Results: A. schaalii preferentially localized to eccrine-associated structures and induced robust IL-17 and IL-1β expression, closely mirroring immune signatures of early human HS. Colonization resulted in marked infiltration of GDT cells and neutrophils compared with commensal and PBS controls. In addition, A. schaalii exposure significantly increased leukotriene B4 (LTB4) production and upregulated 5-lipoxygenase expression (5-LO), implicating lipid mediator pathways associated with heightened neutrophilic inflammation and disease severity in women.
Conclusion: These findings identify Actinotignum schaalii as a novel microbial trigger of early HS that promotes GDT cell-driven IL-17 inflammation and LTB4-mediated innate amplification. This microbial-GDT-lipid mediator axis may contribute to sex-biased disease susceptibility and represents a promising target for early intervention in HS
