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

Br J Dermatol. 2018 Aug;179(2):260-272. doi: 10.1111/bjd.16561. Epub 2018 Jun 11.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Autoimmune Diseases / epidemiology
  • Autoimmune Diseases / immunology*
  • Comorbidity
  • Hair Follicle / cytology
  • Hair Follicle / immunology
  • Hair Follicle / pathology*
  • Hidradenitis Suppurativa / blood
  • Hidradenitis Suppurativa / epidemiology
  • Hidradenitis Suppurativa / immunology*
  • Hidradenitis Suppurativa / pathology
  • Humans
  • Interleukin-17 / blood
  • Lymphocyte Count
  • Obesity / complications
  • Obesity / immunology
  • Smoking / adverse effects
  • Smoking / immunology
  • Stem Cells / immunology
  • Stem Cells / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*

Substances

  • Interleukin-17