Br J Dermatol 2018 Aug 11;179(2):260-272. Epub 2018 Jun 11.
Department of Dermatology and Allergy, Ludwig-Maximilian-University of Munich, Munich, Germany.
Background: Disintegration 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.
Objectives: In 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.
Methods: PubMed-listed, peer-reviewed original research articles characterizing Th17/Treg regulation in HS/acne inversa and associated comorbidities were selected for this review.
Results: This 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.
Conclusions: HS 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.
Imbalanced Th17/Treg axis in hidradenitis suppurativa, B.C. Melnik et al.