Antihistaminic drug olopatadine downmodulates T cell chemotaxis toward CXCL10 by reducing CXCR3 expression, F-actin polymerization and calcium influx in patients with alopecia areata

Alopecia areata (AA) is considered to be a tissue-specific, T cell-mediated autoimmune disease [ [1] Ito T. Hair follicle is a target of stress hormone and autoimmune reactions. J Dermatol Sci. 2010; 60: 67-73 Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar ]. In the acute phase of AA, CD4+ and CD8+ T cells accumulate around the hair bulbs, exhibiting histopathologically characteristic "swarm of bees". An AA rat model develops complete hair regrowth after depletion of either CD4+ or CD8+ T cells [ [2] McElwee K.J. Spiers E.M. Oliver R.F. Partial restoration of hair growth in the DEBR model for alopecia areata after in vivo depletion of CD4+ T cells. Br J Dermatol. 1999; 140: 432-437 Crossref PubMed Scopus (73) Google Scholar ]. Autoantigens in hair follicles, such as melanin-associated proteins, may be recognized preferentially by the accumulated autoreactive T cells [ [3] Gilhar A. Etzioni A. Paus R. Alopecia areata. N Engl J Med. 2012; 366: 1515-1525 Crossref PubMed Scopus (349) Google Scholar ], and the chemokine–chemokine receptor engagement plays a crucial role. Th1-associated, IFN-γ-induced expression of CXCL9 and CXCL10 is seen in AA lesions [ [4] Nakamura M. Jo J. Tabata Y. Ishikawa O. Controlled delivery of T-box21 small interfering RNA ameliorates autoimmune alopecia (Alopecia Areata) in a C3H/HeJ mouse model. Am J Pathol. 2008; 172: 650-658 Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar ]. We found that CXCL10 expression is upregulated in skin lesions of acute phase AA and that T cells expressing CXCR3 (receptor for CXCL10) isolated from the patients have a high velocity toward CXCL10, thereby promoting chemotaxis of CXCR3+ Th1 and Tc1 cells toward the hair bulbs [ [5] Ito T. Hashizume H. Shimauchi T. Funakoshi A. Ito N. Fukamizu H. et al. CXCL10 produced from hair follicles induces Th1 and Tc1 cell infiltration in the acute phase of alopecia areata followed by sustained Tc1 accumulation in the chronic phase. J Dermatol Sci. 2013; 69: 140-147 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar ]. Thus, both augmented chemokine expression and T cell velocity induce "swarm of bees", and inhibition of T cell chemoattraction is a possible therapeutic strategy for AA.