Pro-inflammatory V delta 1(+)T-cells infiltrates are present in and around the hair bulbs of non-lesional and lesional alopecia areata hair follicles

Uchida, Youhei; Gherardini, Jennifer; Schulte-Mecklenbeck, Andreas; Alam, Majid; Cheret, Jeremy; Rossi, Alfredo; Kanekura, Takuro; Gross, Catharina C.; Arakawa, Akiko; Gilhar, Amos; Bertolini, Marta und Paus, Ralf (2020): Pro-inflammatory V delta 1(+)T-cells infiltrates are present in and around the hair bulbs of non-lesional and lesional alopecia areata hair follicles. In: Journal of Dermatological Science, Bd. 100, Nr. 2: S. 129-138

Abstract

Background: It is widely accepted that NKG2D(+)cells are critically involved in alopecia areata (AA) pathogenesis. However, besides being expressed in CD8(+)T-cells and NK cells, NKG2D is also found in human gamma delta T-cells. AA lesional hair follicles (HFs) overexpress NKG2D and gamma delta TCR activating ligands, e.g. MICA and CD1d, and chemoattractants for gamma delta T-cells, such as CXCL10. Objective: To investigate whether abnormal activities of gamma delta T-cells may be involved in AA pathogenesis. Methods: We analyzed the number and activation status of gamma delta T-cells in human healthy, lesional and non-lesional AA scalp biopsies by FACS and/or quantitative (immuno-)histomorphometry. Results: In healthy human scalp skin, the few skin-resident gamma delta T-cells were found to be mostly V delta 1(+), non-activated (CD69 NKG2D (dim)) and positive for CXCL10, and CXCL12 receptors. These V delta 1(+)T-cells predominantly localized in/around the HF infundibulum. In striking contrast, the number of V delta 1(+)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-gamma and lower CD200R expression. Importantly, more pro-inflammatory V delta 1(+)T-cells were seen also around non-lesional AA HFs. Lesional AA HFs also showed significantly higher expression of CXCL12. Conclusion: Our pilot study introduces skin-resident gamma delta T-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-gamma-releasing cells already around non-lesional AA HFs suggest that V delta 1(+)T-cells are involved in the early stages of human AA pathobiology, and may thus deserve therapeutic targeting for optimal AA management. (C) 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0923-1811
• Sprache: Englisch