Prurigo Nodularis Is Characterized by Systemic and Cutaneous T Helper 22 Immune Polarization.

Journal Article (Journal Article)

Prurigo nodularis (PN) is an understudied, chronic inflammatory skin disease that disproportionately affects African Americans and presents with intensely pruritic nodules of unknown etiology. To better characterize the immune dysregulation in PN, PBMCs and skin biopsies were obtained from patients with PN and healthy subjects (majority African American) matched by age, race, and sex. Flow cytometric analysis of functional T-cell response comparing patients with PN with healthy subjects identified increased γδT cells (CD3+CD4-CD8-γδTCR+) and Vδ2+ γδT enrichment. Activated T cells demonstrated uniquely increased IL-22 cytokine expression in patients with PN compared with healthy controls. CD4+ and CD8+ T cells were identified as the source of increased circulating IL-22. Consistent with these findings, RNA sequencing of lesional PN skin compared with nonlesional PN skin and biopsy site‒matched control skin demonstrated robust upregulation of T helper (Th) 22‒related genes and signaling networks implicated in impaired epidermal differentiation. Th22‒related cytokine upregulation remained significant, with stratifications by race and biopsy site. Importantly, the expression of the IL-22 receptors IL22RA1 and IL22RA2 was significantly elevated in lesional PN skin. These results indicate that both systemic and cutaneous immune responses in patients with PN are skewed toward a Th22/IL-22 profile. PN may benefit from immunomodulatory therapies directed at Th22‒mediated inflammation.

Full Text

Duke Authors

Cited Authors

  • Belzberg, M; Alphonse, MP; Brown, I; Williams, KA; Khanna, R; Ho, B; Wongvibulsin, S; Pritchard, T; Roh, YS; Sutaria, N; Choi, J; Jedrych, J; Johnston, AD; Sarkar, K; Vasavda, C; Meixiong, J; Dillen, C; Bondesgaard, K; Paolini, JF; Chen, W; Corcoran, D; Devos, N; Kwatra, MM; Chien, AL; Archer, NK; Garza, LA; Dong, X; Kang, S; Kwatra, SG

Published Date

  • September 2021

Published In

Volume / Issue

  • 141 / 9

Start / End Page

  • 2208 - 2218.e14

PubMed ID

  • 33771530

Pubmed Central ID

  • PMC8384659

Electronic International Standard Serial Number (EISSN)

  • 1523-1747

Digital Object Identifier (DOI)

  • 10.1016/j.jid.2021.02.749

Language

  • eng

Conference Location

  • United States