T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities

Abstract

BackgroundDisintegration of the infundibula of terminal hair follicles (HFs) in intertriginous skin areas exhibits the histological hallmark of hidradenitis suppurativa (HS)/acne inversa, featuring a dissecting terminal hair folliculitis. Elevated serum levels of interleukin (IL)-17 and local increase in the ratio of proinflammatory T helper (Th)17 cells and anti-inflammatory regulatory T cells (Tregs) have been reported. Perifollicular Tregs play a key role in HF stem cell homeostasis and infundibular integrity. ObjectivesIn this review, we evaluate the Th17/Treg ratio in HS, its aggravating conditions and associated comorbidities. Furthermore, we intended to clarify whether drugs with reported beneficial effects in the treatment of HS readjust the deviated Th17/Treg axis. MethodsPubMed-listed, peer-reviewed original research articles characterizing Th17/Treg regulation in HS/acne inversa and associated comorbidities were selected for this review. ResultsThis review presents HS as a disease that exhibits an increased Th17/Treg ratio. 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 and decreased Notch signalling. In addition, HS-associated autoimmune diseases exhibit a disturbed Th17/Treg axis resulting in a Th17-dominant state. All drugs that have beneficial effects in the treatment of HS normalize the Th17/Treg ratio. ConclusionsHS immunopathogenesis is closely related to deviations of the Th17/Treg balance, which may negatively affect Treg-controlled HF stem cell homeostasis and infundibular integrity. Pharmacological intervention should not only attenuate Th17/IL-17 signalling, but should also improve Treg function in order to stabilize HF stem cell homeostasis and infundibular integrity. What's already known about this topic? A recent study observed an increased T helper (Th)17/regulatory T-cell (Treg) ratio in hidradenitis suppurativa (HS) skin lesions. Dissection of the infundibulum of terminal hair follicles (HFs) plays a key role in early pathogenesis of HS. Tregs play a key role in HF stem cell homeostasis. HS is associated with an increased prevalence of autoimmune comorbidities. The mode of action of various drugs in the treatment of HS remains obscure. What does this study add? The translational link between increases in the Th17/Treg ratio in HS and disturbed HF stem cell homeostasis provides a new explanation for dissecting terminal hair folliculitis. 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, suggesting a systemic character of HS. Therapeutic interventions should augment Treg differentiation and attenuate Th17 polarization.