Hidradenitis Suppurativa Is Characterized by Dysregulation of the Th17:Treg Cell Axis, Which Is Corrected by Anti-TNF Therapy

• Published in: Journal of investigative dermatology Vol. 137; no. 11; pp. 2389 - 2395
• Main Authors: Moran, Barry, Sweeney, Cheryl M., Hughes, Rosalind, Malara, Anna, Kirthi, Shivashini, Tobin, Anne-Marie, Kirby, Brian, Fletcher, Jean M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2017
• Subjects: Adult; Biopsy, Needle; Case-Control Studies; Cells, Cultured - drug effects; Cohort Studies; Female; Hidradenitis Suppurativa - drug therapy; Hidradenitis Suppurativa - immunology; Hidradenitis Suppurativa - pathology; Humans; Immunity, Cellular - drug effects; Immunity, Cellular - physiology; Immunohistochemistry; Interleukin-17 - immunology; Interleukin-17 - metabolism; Male; Reference Values; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Th17 Cells - immunology; Th17 Cells - metabolism; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - pharmacology; PBS; PG; Treg; Th cell; HS; PBMC; TNF
• ISSN: 0022-202X; 1523-1747; 1523-1747
• DOI: 10.1016/j.jid.2017.05.033

Hidradenitis suppurativa (HS) is a chronic, inflammatory, and debilitating disease of hair follicles with 1–4% prevalence and high morbidity. There is a dearth of information on the pathogenesis and immune dysregulation underlying HS; therefore, we carried out a detailed analysis of skin-infiltrating T cells. Cells isolated from skin biopsy samples and blood from HS patients and healthy control subjects were analyzed by 16-parameter flow cytometry to provide detailed profiles of CD4 T-cell subsets. We observed substantial infiltration of inflammatory T cells with a striking T helper (Th) type 17-skewed cytokine profile in HS skin; these cells expressed the Th17 lineage marker CD161 and IL-17, as well as proinflammatory cytokines GM-CSF, IL-22, IFN-γ, and tumor necrosis factor. Regulatory T cells were also enriched in HS lesional skin; however, the ratio of Th17 to regulatory T cells was nonetheless highly dysregulated in favor of Th17 cells. In contrast, lesional skin from anti-tumor necrosis factor–treated HS patients who showed substantial clinical improvement exhibited a significant reduction in the frequency of Th17 cells and normalization of the Th17 to regulatory T cell ratio. These data suggest that inhibition of pathogenic IL-17 via tumor necrosis factor blockade is associated with improvement in immune dysregulation in HS and may provide a rationale for targeting IL-17 in the disease.