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Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa
Author(s) -
Kelly G.,
Hughes R.,
McGarry T.,
Born M.,
Adamzik K.,
Fitzgerald R.,
Lawlor C.,
Tobin A.M.,
Sweeney C.M.,
Kirby B.
Publication year - 2015
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.14075
Subject(s) - pathogenesis , cytokine , hidradenitis suppurativa , immunology , medicine , interleukin , caspase 1 , cd14 , immune system , cd11c , flow cytometry , tumor necrosis factor alpha , inflammation , pathology , biology , inflammasome , disease , phenotype , biochemistry , gene
Summary Background There is a dearth of information on the precise pathogenesis of hidradenitis suppurativa ( HS ), but immune dysregulation is implicated. Objectives To determine the nature of the immune response in HS . Methods Skin biopsies – lesional, perilesional (2 cm away) and uninvolved (10 cm away) – were obtained from patients with HS and healthy controls. The expression of various cytokines was determined by enzyme‐linked immunosorbent assay, flow cytometry and real‐time polymerase chain reaction. Results The expression of the inflammatory cytokines interleukin ( IL )‐17, IL ‐1β and tumour necrosis factor‐α was enhanced in lesional skin of patients with HS . In addition, IL 17A and IL 1B mRNA were enhanced in clinically normal perilesional skin. CD 4 + T cells produced IL ‐17 in HS , while CD 11c + CD 1a − CD 14 + cells were sources of IL ‐1β. Activated caspase‐1 was detected in HS skin and was associated with enhanced expression of NLRP 3 and IL 18 . Inhibition of caspase‐1 decreased IL ‐1β and IL ‐18 production, suggesting that the caspase‐1 pathway participates in IL ‐1β and IL ‐18 expression in HS . Abnormal cytokine expression was detected in perilesional and uninvolved skin, which may suggest that subclinical inflammation is present in HS skin prior to the formation of an active lesion. Conclusions This study demonstrates that CD 4 + T cells produce IL ‐17 in HS and that the IL ‐17 pathway may be important in HS pathogenesis. CD 11c + CD 1a − CD 14 + cells are a source of IL ‐1β in HS , the production of which was shown to be mediated, in part, via a caspase‐1‐dependent pathway. These results suggest that IL ‐17 and the caspase‐1‐associated cytokines IL ‐1β and IL ‐18 may play a role in the pathogenesis of HS .