Regulatory T cell subsets in bullous pemphigoid and dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid

J Dermatol Sci. 2020 Oct;100(1):23-30. doi: 10.1016/j.jdermsci.2020.08.004. Epub 2020 Aug 15.


Background: Regulatory T (Treg) cells play an essential role in peripheral immune tolerance. Bullous pemphigoid (BP) is the most common blistering disease and is caused by autoantibodies to two BP antigens: type XVII collagen and BP230. Recently, we reported that Treg cell dysfunction may cause the production of autoantibodies to BP antigens. Several studies have suggested an association between Treg cells and BP pathogenesis. However, Treg cells are heterogeneous in humans, leading to inconsistent results in previous studies.

Objective: To assess functional Treg subsets in BP.

Methods: We examined three distinct Treg subsets in conventional BP (cBP) patients before versus after systemic corticosteroid treatment, dipeptidyl peptidase-4 inhibitor-associated BP (DPP-4i-BP) patients, younger controls and older controls.

Results: We found that total Treg cells and all Treg cell subsets were increased in cBP patients before treatment and decreased by systemic corticosteroid treatment. In contrast, neither total Treg cells nor all Treg subsets were increased in DPP-4i-BP. Notably, CD45RA- Foxp3hi effector Treg cells positively correlated with disease severity in cBP, whereas CD45RA+Foxp3lo naïve Treg cells positively correlated with the disease severity in DPP-4i-BP.

Conclusion: These findings suggest that Treg cells are differently involved in the pathogeneses of cBP and DPP-4i-BP.

Keywords: Bullous pemphigoid; Bullous pemphigoid disease area index; CD45RA; DPP-4 inhibitor; Regulatory T cell subset.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / immunology*
  • Autoantibodies / metabolism
  • Autoantigens / immunology
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Collagen Type XVII
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects*
  • Dystonin / immunology
  • Female
  • Glucocorticoids / administration & dosage
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Non-Fibrillar Collagens / immunology
  • Pemphigoid, Bullous / blood
  • Pemphigoid, Bullous / chemically induced
  • Pemphigoid, Bullous / diagnosis
  • Pemphigoid, Bullous / immunology*
  • Severity of Illness Index
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism


  • Autoantibodies
  • Autoantigens
  • DST protein, human
  • Dipeptidyl-Peptidase IV Inhibitors
  • Dystonin
  • Glucocorticoids
  • Non-Fibrillar Collagens