Transcriptomic Landscape of Prurigo Nodularis Lesional Skin CD3+ T Cells Using Single-Cell RNA Sequencing

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by symmetrically distributed, widespread, pruritic nodules occurring in patients with chronic pruritus and may be associated with a history of atopic dermatitis (AD) ( Pereira et al., 2018 Pereira M.P. Steinke S. Zeidler C. Forner C. Riepe C. Augustin M. et al. European academy of dermatology and venereology European prurigo project: expert consensus on the definition, classification and terminology of chronic prurigo. J Eur Acad Dermatol Venereol. 2018; 32: 1059-1065 Crossref PubMed Scopus (134) Google Scholar ). The lack of approved therapies and the limited efficacy of off-label treatments reflect the poor understanding of PN pathogenesis ( Williams et al., 2020 Williams K.A. Huang A.H. Belzberg M. Kwatra S.G. Prurigo nodularis: pathogenesis and management. J Am Acad Dermatol. 2020; 83: 1567-1575 Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar ). Previous studies have suggested roles for neuronal dysregulation, aberrant keratinocyte signaling, and underlying immune activation ( Fukushi et al., 2011 Fukushi S. Yamasaki K. Aiba S. Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis. Br J Dermatol. 2011; 165: 990-996 Crossref PubMed Scopus (80) Google Scholar ; Haas et al., 2010 Haas S. Capellino S. Phan N.Q. Böhm M. Luger T.A. Straub R.H. et al. Low density of sympathetic nerve fibers relative to substance P-positive nerve fibers in lesional skin of chronic pruritus and prurigo nodularis. J Dermatol Sci. 2010; 58: 193-197 Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar ; Wong et al., 2020 Wong L.S. Yen Y.T. Lin S.H. Lee C.H. IL-17A induces endothelin-1 expression through p38 pathway in prurigo nodularis. J Invest Dermatol. 2020; 140: 702-706.e2 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar ). Targeted real-time RT-qPCR, immunohistochemical staining, RNA sequencing, and clinical studies have suggested that PN has variable amounts of T helper (Th) 2, Th17, or Th22 signaling ( Belzberg et al., 2021 Belzberg M. Alphonse M.P. Brown I. Williams K.A. Khanna R. Ho B. et al. Prurigo nodularis is characterized by systemic and cutaneous T helper 22 immune polarization. J Invest Dermatol. 2021; 141: 2208-2218.e14 Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar ; Calugareanu et al., 2020 Calugareanu A. Jachiet M. Tauber M. Nosbaum A. Aubin F. Misery L. et al. Effectiveness and safety of dupilumab for the treatment of prurigo nodularis in a French multicenter adult cohort of 16 patients. J Eur Acad Dermatol Venereol. 2020; 34: e74-e76 Crossref PubMed Scopus (55) Google Scholar ; Fukushi et al., 2011 Fukushi S. Yamasaki K. Aiba S. Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis. Br J Dermatol. 2011; 165: 990-996 Crossref PubMed Scopus (80) Google Scholar ; Park et al., 2011 Park K. Mori T. Nakamura M. Tokura Y. Increased expression of mRNAs for IL-4, IL-17, IL-22 and IL-31 in skin lesions of subacute and chronic forms of prurigo. Eur J Dermatol. 2011; 21: 135-136 Crossref PubMed Scopus (38) Google Scholar ; Tsoi et al., 2022 Tsoi L.C. Hacini-Rachinel F. Fogel P. Rousseau F. Xing X. Patrick M.T. et al. Transcriptomic characterization of prurigo nodularis and the therapeutic response to nemolizumab. J Allergy Clin Immunol. 2022; 149: 1329-1339 Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar ; Wong et al., 2020 Wong L.S. Yen Y.T. Lin S.H. Lee C.H. IL-17A induces endothelin-1 expression through p38 pathway in prurigo nodularis. J Invest Dermatol. 2020; 140: 702-706.e2 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar ).