Th17/Treg imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking, and autoimmune comorbidities B.C. Melnik1, S.M. John1, W. Chen2, and G. Plewig3 1Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück, Germany 2Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany 3Department of Dermatology and Allergy, Ludwig-Maximilian-University of Munich, Munich, Germany British Journal of Dermatology. DOI: 10.1111/bjd.16561.

Bodo C. Melnik, University of Osnabrück, Germany

Introduction What’s already known? A recent study by Barry Moran in the J. Invest. Dermatol. reported a deviated Th17/Treg axis in skin lesions of hidradenitis suppurativa (HS). Dissection of the infundibulum of terminal hair follicles plays a key role in early pathogenesis. HS is associated with an increased prevalence of autoimmune comorbidities. The mode of action of various drugs in the treatment of HS remains obscure.

Objective Our study evaluates the Th17/Treg ratio in HS, its aggravating conditions and associated comorbidities. This study tries to clarify whether drugs with reported beneficial effects in HS readjust the deviated Th17/Treg axis.

Methods PubMed-listed, peer-reviewed original research articles characterizing Th17/Treg regulation in HS and associated comorbidities have been selected until March 2018. All papers have been evaluated by means of translational research.

Results Our study presents HS as a disease exhibiting a disturbed Th17/Treg balance. Perifollicular deficiencies in Treg numbers or function may disturb HF stem cell homeostasis initiating infundibular dissection of terminal HFs and perifollicular inflammation. The Th17/Treg imbalance is aggravated by obesity, smoking as well as decreased Notch signalling. In addition, HS-associated autoimmune diseases exhibit a disturbed Th17/Treg axis. All drugs that have beneficial effects in the treatment of HS normalise the Th17/Treg imbalance.

Results Working model of Th17/Treg imbalance in the pathogenesis of HS Normal Normal Th17/Treg axis controls hair follicle stem cell homeostasis HS Th17-dominated Th17/Treg axis disturbs Treg-mediated hair follicle stem cell homeostasis and infundibular integrity promoting the dissecting terminal hair folliculitis

Results Comorbidities of HS associated with an increased Th17/Treg ratio

Results Therapeutic intervention in HS either decreases Th17 or enhances Treg cell numbers

Discussion Future research should clarify whether the increase in the Th17/Treg ratio and Treg-related disturbances of HF stem cell homeostasis may explain the primary pathogenesis of HS or whether these deviations are a secondary phenomenon. Genetic polymorphisms or functional aberrations of either FoxP3- and/or RORγt expression including aberrations of their posttranslational regulatory cofactors might be on the path to induce the imbalance of Th17/Treg in HS.

Conclusions What does this study add? The deviatedTh17/Treg ratio in HS may induce disturbances of HF stem cell homeostasis promoting the dissecting terminal hair folliculitis of HS. Obesity and smoking increase the Th17/Treg ratio. Deficient-secretase/Notch signalling in familial HS may impair Treg-facilitated HF stem cell homeostasis. HS-associated comorbidities exhibit an increased Th17/Treg ratio pointing to a systemic character of HS. Therapeutic interventions should augment Treg differentiation and attenuate Th17 polarization.  

From left to right: Prof. WenChieh Chen, Prof. Gerd Plewig and Prof From left to right: Prof. WenChieh Chen, Prof. Gerd Plewig and Prof. Bodo Melnik

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