Pro-inflammatory Vδ1+T-cells infiltrate in and around the hair bulbs of non-lesional and lesional alopecia areata hair follicles

Abstract Background It is widely accepted that NKG2D+cells are involved in alopecia areata (AA) pathogenesis. However, besides being expressed in CD8+T-cells and NK cells, NKG2D is also found in human γδT-cells. AA lesional hair follicles (HFs) overexpress activating ligands for γδTCR and chemoattractants for γδT-cells, such as CXCL10. Objective To investigate whether abnormal activities of γδT-cells may be involved in AA pathogenesis. Methods We analyzed the number and activation status of γδT-cells in human healthy, lesional and non-lesional human AA scalp biopsies by FACS and/or quantitative (immuno-)histomorphometry. Results In healthy human scalp skin, the few skin-resident γδT-cells were found to be mostly Vδ1+, non-activated (CD69−NKG2Ddim) and positive for CXCL10, and CXCL12 receptors. These γδT-cells, namely Vδ1+, predominantly localized in/around the HF infundibulum. In striking contrast, the number of Vδ1+T-cells was significantly higher around and even inside the proximal (suprabulbar and bulbar) epithelium of lesional AA HFs. These cells also showed a pro-inflammatory phenotype, i.e. higher NKG2D, and IFN-γ and lower CD200R expression. Importantly, more pro-inflammatory Vδ1+T-cells were seen also around non-lesional AA HFs. We revealed here that AA lesional HFs also showed significant higher expression of CXCL12. Conclusion Our pilot study introduces skin-resident γδT-cells as a previously overlooked, but potentially important, mostly (auto-)antigen-independent, new innate immunity protagonist in AA pathobiology. The HF infiltration of these activated IFN-γ-releasing cells already around non-lesional AA HFs suggest that Vδ1+T-cells are involved in the early stages of human AA pathobiology, and may thus deserve therapeutic targeting for optimal AA management.