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 that occurs 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 JEADV. 2018 Jul; 32: 1059-1065 Crossref PubMed Scopus (0) 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 Dec; 83: 1567-1575 Abstract Full Text Full Text PDF PubMed Google Scholar ). Previous studies have suggested roles for neuronal dysregulation, aberrant keratinocyte signaling, and underlying immune activation ( 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 Jun; 58: 193-197 Abstract Full Text Full Text PDF PubMed Scopus (0) 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 Nov; 165: 990-996 Crossref PubMed Scopus (66) Google Scholar ; Wong et al., 2020 Wong LS, Yen YT, Lin SH, Lee CH. IL-17A Induces Endothelin-1 Expression through p38 Pathway in Prurigo Nodularis. J Invest Dermatol. 2020 Mar;140(3):702-706.e2. Google Scholar ). Targeted real-time PCR, immunohistochemical staining, RNA-sequencing as well as clinical studies have suggested that PN has variable amounts of T helper(Th)2, Th17, or Th22 signaling ( 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 Nov; 165: 990-996 Crossref PubMed Scopus (66) 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 EJD. 2011; 21: 135-136 Crossref PubMed Scopus (0) 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 JEADV. 2020 Feb; 34: e74-e76 Crossref PubMed Scopus (0) Google Scholar ; Wong et al., 2020 Wong LS, Yen YT, Lin SH, Lee CH. IL-17A Induces Endothelin-1 Expression through p38 Pathway in Prurigo Nodularis. J Invest Dermatol. 2020 Mar;140(3):702-706.e2. Google Scholar ; Belzberg et al., 2021 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. 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 Apr; 149: 1329-1339 Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar ).