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

Publication ,  Journal Article
Belzberg, M; Alphonse, MP; Brown, I; Williams, KA; Khanna, R; Ho, B; Wongvibulsin, S; Pritchard, T; Roh, YS; Sutaria, N; Choi, J; Jedrych, J ...
Published in: J Invest Dermatol
September 2021

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.

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Published In

J Invest Dermatol

DOI

EISSN

1523-1747

Publication Date

September 2021

Volume

141

Issue

9

Start / End Page

2208 / 2218.e14

Location

United States

Related Subject Headings

  • Up-Regulation
  • T-Lymphocytes, Helper-Inducer
  • Skin
  • Sequence Analysis, RNA
  • Receptors, Interleukin
  • Prurigo
  • Middle Aged
  • Male
  • Lymphocyte Activation
  • Interleukins
 

Citation

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Belzberg, M., Alphonse, M. P., Brown, I., Williams, K. A., Khanna, R., Ho, B., … Kwatra, S. G. (2021). Prurigo Nodularis Is Characterized by Systemic and Cutaneous T Helper 22 Immune Polarization. J Invest Dermatol, 141(9), 2208-2218.e14. https://doi.org/10.1016/j.jid.2021.02.749
Belzberg, Micah, Martin Prince Alphonse, Isabelle Brown, Kyle A. Williams, Raveena Khanna, Byron Ho, Shannon Wongvibulsin, et al. “Prurigo Nodularis Is Characterized by Systemic and Cutaneous T Helper 22 Immune Polarization.J Invest Dermatol 141, no. 9 (September 2021): 2208-2218.e14. https://doi.org/10.1016/j.jid.2021.02.749.
Belzberg M, Alphonse MP, Brown I, Williams KA, Khanna R, Ho B, et al. Prurigo Nodularis Is Characterized by Systemic and Cutaneous T Helper 22 Immune Polarization. J Invest Dermatol. 2021 Sep;141(9):2208-2218.e14.
Belzberg, Micah, et al. “Prurigo Nodularis Is Characterized by Systemic and Cutaneous T Helper 22 Immune Polarization.J Invest Dermatol, vol. 141, no. 9, Sept. 2021, pp. 2208-2218.e14. Pubmed, doi:10.1016/j.jid.2021.02.749.
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. Prurigo Nodularis Is Characterized by Systemic and Cutaneous T Helper 22 Immune Polarization. J Invest Dermatol. 2021 Sep;141(9):2208-2218.e14.
Journal cover image

Published In

J Invest Dermatol

DOI

EISSN

1523-1747

Publication Date

September 2021

Volume

141

Issue

9

Start / End Page

2208 / 2218.e14

Location

United States

Related Subject Headings

  • Up-Regulation
  • T-Lymphocytes, Helper-Inducer
  • Skin
  • Sequence Analysis, RNA
  • Receptors, Interleukin
  • Prurigo
  • Middle Aged
  • Male
  • Lymphocyte Activation
  • Interleukins