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IL-21 Might Promote Psoriatic Inflammation

Interleukin (IL)-21 may promote psoriatic inflammation by inducing imbalance in Th17 and Treg cell populations, a new study found. IL-21 and IL-21 receptor (IL-21R) expression in normal and psoriatic lesional skin were determined by immunohistochemical staining, immunofluorescence staining, and western blotting. The levels of IL-21, IL-17A, and IL-22 in the culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Researchers found:

  • IL-21 and IL-21R were highly expressed in the lesional skin and peripheral blood of patients with psoriasis.
  • IL-21 promoted CD4+ T cells proliferation and Th17 cells differentiation, inhibiting Treg cells differentiation by upregulation RORγt expression, and downregulating Foxp3 expression, with increased expression and secretion of IL-17A and IL-22.
  • The proportion of Treg cells was negatively correlated with that of Th17 cells in patients with psoriasis.


Shi Y, et al. IL-21 induces an imbalance of Th17/Treg cells in moderate-to-severe plaque psoriasis patients. [Published online ahead of print August 7, 2019]. Front Immunol. doi: 10.3389/fimmu.2019.01865.


There are several cytokines implicated in the pathogenesis of psoriasis including tumor necrosis factor, IL-17, IL-23 which are targeted by several biologic agents. The data in this report suggest that IL-21 promotes CD4 T cell proliferation and enhances the differentiation and function of Th17 cells. Other studies have demonstrated that IL-21 plays a vital role in several autoimmune diseases including rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. The fact that IL-21 also downregulates the differentiation of Treg cells suggests that this cytokine may a be a potential therapeutic target in psoriasis. —Paul S. Yamauchi, MD, PhD; Clinical Assistant Professor of Dermatology David Geffen School of Medicine at UCLA; Harbor-UCLA Medical Center Division of Dermatology; Adjunct Associate Professor John Wayne Cancer Institute.