Investigations revealed the significance of the overlooked population of T-cells—the Gamma-delta-T-cells (γδT-cells)—in Alopecia Areata pathogenesis1

Our skin contains a varied population of T-cells, the crucial elements of the immune system that perform surveillance on specific foreign bodies. Even so, sometimes instead of protecting, they turn into a self-attacking mode, which is seen in the case of Alopecia Areata (AA)—a hair loss disorder, where T-cells damage hair follicles (HFs) causing patchy to total hair loss. A previous study showed that both αβT and NK cells are key players in the development and perpetuation of this disease, and these cells can be found within HFs of affected regions (2). It was known that IFN-γ-producing CD8+ T cells that are found within affected HFs express NKG2D and also overexpress CD1d and CXCL10 (a chemoattractant for γδT cells).

Therefore, in our current study published in the Journal of Dermatological Science (1), we investigated the functional role of γδT-cells and its contribution to the pathogenesis of AA. The researchers looked into the activation status of γδT-cells in a clinically relevant human scalp skin in vivo model by FACS analysis. Moreover, by quantitative immuno-histomorphometry, they compared relevant subpopulations of γδT-cells in healthy human scalp skin with those in lesional and non-lesional human AA scalp biopsies. They also investigated whether a sub-population of γδT-cells, called Vδ1+T-cells, found to be present in or around AA-affected HFs, feature a pro-inflammatory phenotype by expressing NKG2D, IFN-γ – or any of the critical cytokines implicated in AA pathology.

One of the leading authors, Dr Bertolini mentioned, “We provided the first evidence that lesional HFs in scalp biopsies from AA patients exhibit a significantly higher number of both peri- and intra-follicular γδT-cells—primarily Vδ1+T-cells.”

These γδT cells were confined to the infundibulum region, both within the perifollicular dermis or intra-follicular epithelium. The deeper, immune-privileged bulb area of the HF did not contain any γδT cells. They exhibited canonical pro-inflammatory makeup with higher levels of NKG2D and IFN-γ. Strengthening the pro-inflammatory status, the Vδ1+T-cells also feature lower expression of the vital immunoinhibitory receptor CD200R. Conspicuously, more pro-inflammatory Vδ1+T-cells were also seen around non-lesional AA HFs. At the same time, the lesional AA HFs displayed an upregulation of chemoattractant, CXCL12. This means elevated levels of CXCL12 could readily attract its receptor (CXCR4) on γδT-cells—another pro-inflammatory hallmark.

Dr Bertolini added, “We envision a follow-up study with a larger number of AA patients. Another puzzle remains to be solved, can the pro-inflammatory Vδ1+T-cells alone cause AA lesions in human skin?”

In conclusion, this study points to another key player in the pathology of AA: skin-resident γδT cells and sheds new light on AA pathobiology from a distinctive angle, which has so far been rather overlooked. It will be important to further dissect the role of these cells in AA to optimize therapeutic strategies for the management of the disease.

References:

1. Uchida Y et al,. “Pro-inflammatory Vδ1(+)T-cells infiltrates are present in and around the hair bulbs of non-lesional and lesional alopecia areata hair follicles” Journal of dermatological science. Sep 18 2020;doi:10.1016/j.jdermsci.2020.09.001

2. Ito T et al., “Recent advances in the pathogenesis of autoimmune hair loss disease alopecia areata” Clinical & developmental immunology. 2013;2013:348546. doi:10.1155/2013/348546