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

Background: Alopecia areata (AA) is an organ-specific and cell-mediated autoimmune disease. T lymphocytes densely surround lesional hair bulbs, which is histologically referred to as "swarm of bees". However, pathomechanisms of "swarm of bees" are still uncertain. Objective: We investigated the pathological mechanisms of "swarm of bees", focusing on T-cell chemotaxis so that inhibition of chemotaxis may be strong candidate of novel treatments for AA. Methods: We investigate the expression of chemokine receptors on T cells obtained from peripheral blood mononuclear cells (PBMCs) and skin infiltrating cells in AA patients. In addition, real-time chemotaxis assay was also demonstrated. Results: In PBMCs, the frequency of CXCR3(+)CD4(+) T cells (Th1) was significantly higher in acute-phase AA than in chronic-phase AA or healthy control, while CXCR3(+)CD8(+) T cells (Tc1) were significantly increased in chronic-phase AA. 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. Immunohistochemical and real-time RT-PCR studies demonstrated that hair follicles of acute-phase AA expressed a high level of Th1-associated chemokine CXCL10. By chemotaxis assay, freshly isolated PBMCs from acute-phase AA patients had a strong velocity of chemotaxis toward CXCL10 with increased expression of F-actin. Conclusions: These results suggest that the increased production of CXCL10 from hair follicles induces preferential infiltrates of highly chemoattracted Th1 and Tc1 cells in the acute phase of AA, and Tc1 infiltration remains prolonged in the chronic phase. (c) 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.