Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa.
BACKGROUND
There is a dearth of information on the precise pathogenesis of hidradenitis suppurativa (HS), but immune dysregulation is implicated.


OBJECTIVE
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, IL17A and IL1B mRNA were enhanced in clinically normal perilesional skin. CD4(+) T cells produced IL-17 in HS, while CD11c(+) CD1a(-) CD14(+) cells were sources of IL-1β. Activated caspase-1 was detected in HS skin and was associated with enhanced expression of NLRP3 and IL18. 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 CD4(+) T cells produce IL-17 in HS and that the IL-17 pathway may be important in HS pathogenesis. CD11c(+) CD1a(-) CD14(+) 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.
Dermatology Research, Education and Research Centre, St Vincent's University Hospital, University College Dublin, Dublin 4, Ireland.
G
G
Kelly
Dermatology Research, Education and Research Centre, St Vincent's University Hospital, University College Dublin, Dublin 4, Ireland.
R
R
Hughes
Department of Rheumatology, St Vincent's University Hospital, University College Dublin, Dublin 4, Ireland.|The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
T
T
McGarry
Dermatology Research, Education and Research Centre, St Vincent's University Hospital, University College Dublin, Dublin 4, Ireland.
M
M
van den Born
Department of Dermatology, St Vincent's University Hospital, University College Dublin, Dublin 4, Ireland.
K
K
Adamzik
Department of Dermatology, Adelaide and Meath Hospital, Tallaght, Dublin, Ireland.
R
R
Fitzgerald
Department of Plastic Surgery, St Vincent's University Hospital, University College Dublin, Dublin 4, Ireland.
C
C
Lawlor
Department of Dermatology, Adelaide and Meath Hospital, Tallaght, Dublin, Ireland.
A M
AM
Tobin
Dermatology Research, Education and Research Centre, St Vincent's University Hospital, University College Dublin, Dublin 4, Ireland.
C M
CM
Sweeney
Department of Dermatology, St Vincent's University Hospital, University College Dublin, Dublin 4, Ireland.
B
B
Kirby
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D020170:Caspase 1 / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017497:Hidradenitis Suppurativa / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D020381:Interleukin-17 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000276:immunology*
D015703:Antigens, CD; D016207:Cytokines; D020381:Interleukin-17; D020382:Interleukin-18; D053583:Interleukin-1beta; D012333:RNA, Messenger; D020170:Caspase 1