Th1 Chemokine CXCL10 and Alopecia Areata: The Possible Target for the Treatment of Alopecia Areata

Abstract

Alopecia areata (AA) is an organ-specific and cell-mediated autoimmune disease. Recent studies have suggested the most important effector cell of AA is NKG2D+CD8+T cells, and outer root sheath (ORS) cells highly express NKG2D ligands, such as MICA, in AA lesions. T lymphocytes densely surround lesional hair bulbs, which is histologically referred to as “swarm of bees”. Immunohistochemical and real-time RT-PCR studies reveal that hair follicles of acute-phase AA expressed a high level of Th1-associated chemokine CXCL10. In the skin lesions of acute-phase AA, CXCR3+CD4+ and CXCR3+CD8+ T cells infiltrated in the juxta-follicular area. In chronic-phase AA, CXCR3+CD8+ T cells dominated the infiltrate around hair bulbs, possibly contributing to the prolonged state of hair loss. Lymphocytes obtained from a lesional skin of acute-phase AA contained CXCR3+CD4+ and CXCR3+CD8+ T cells at higher percentages than those of PBMCs, suggesting preferential emigration from the blood. Furthermore, freshly isolated PBMCs from acute-phase AA patients had a strong velocity of chemotaxis toward CXCL10 with increased expression of F-actin. Antihistaminic drugs have been used in Japan, and these have possibility to downregulate chemotactic activity in AA. Olopatadine shows suppressive effects of chemotactic activity in the AA patients’ CD4+ and CD8+ T cells towards CXCL10 by reducing CXCR3 expression, F-actin polymerization, and Ca++ influx. In conclusion, the increased production of CXCL10 from hair follicles induces preferential infiltrates of Th1 and Tc1 cells in the acute phase of AA, and Tc1 infiltration remains prolonged in the chronic phase. Therefore, inhibitory treatment of chemotactic activity might be novel target for the treatment of AA.