Prurigo Nodularis is Characterized by Systemic and Cutaneous Th22 Immune Polarization

• Published in: Journal of investigative dermatology Vol. 141; no. 9; pp. 2208 - 2218.e14
• Main Authors: Belzberg, Micah, Alphonse, Martin Prince, Brown, Isabelle, Williams, Kyle A., Khanna, Raveena, Ho, Byron, Wongvibulsin, Shannon, Pritchard, Thomas, Roh, Youkyung Sophie, Sutaria, Nishadh, Choi, Justin, Jedrych, Jaroslaw, Johnston, Andrew D., Sarkar, Kakali, Vasavda, Chirag, Meixiong, Jimmy, Dillen, Carly, Bondesgaard, Kent, Paolini, John F, Chen, Wei, Corcoran, David, Devos, Nicolas, Kwatra, Madan M., Chien, Anna L., Archer, Nathan K., Garza, Luis A., Dong, Xinzhong, Kang, Sewon, Kwatra, Shawn G.
• Format: Journal Article
• Language: English
• Published: 23.03.2021
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1016/j.jid.2021.02.749

Prurigo nodularis is an understudied, chronic inflammatory skin disease that disproportionately affects African-Americans and presents with intensely pruritic nodules of unknown etiology. To better characterize immune dysregulation in prurigo nodularis, peripheral blood mononuclear cells and skin biopsies were obtained from majority African American patients with prurigo nodularis and healthy subjects matched by age, race, and sex. Flow cytometric analysis of functional T-cell response comparing prurigo nodularis to healthy subjects identified increased γδT-cells (CD3 + CD4 − CD8 − γδTCR + ) with Vδ2 + γδT-enrichment. Activated T-cells demonstrated uniquely increased IL-22 cytokine expression in prurigo nodularis patients when compared to 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 prurigo nodularis skin compared to non-lesional prurigo nodularis skin and biopsy site matched control skin demonstrated robust up-regulation of Th22-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/A2 was significantly elevated in lesional prurigo nodularis skin. These results indicate both systemic and cutaneous immune responses in prurigo nodularis patients are skewed towards a Th22/IL-22 profile. Prurigo nodularis may benefit from immunomodulatory therapies directed at Th22-mediated inflammation.