TY - JOUR
T1 - Pro-inflammatory Vδ1+T-cells infiltrates are present in and around the hair bulbs of non-lesional and lesional alopecia areata hair follicles
AU - Uchida, Youhei
AU - Gherardini, Jennifer
AU - Schulte-Mecklenbeck, Andreas
AU - Alam, Majid
AU - Chéret, Jérémy
AU - Rossi, Alfredo
AU - Kanekura, Takuro
AU - Gross, Catharina C.
AU - Arakawa, Akiko
AU - Gilhar, Amos
AU - Bertolini, Marta
AU - Paus, Ralf
N1 - Funding Information:
The study was supported in part by research grants from National Alopecia Areata Foundation (NAAF, USA) to R.P. and M.B, from Associazione Nazionale Mediterranea Alopecia Areata (ANMAA, Italy) to M.B., by the NIHR Manchester Biomedical Research Centre, “Inflammatory Hair Diseases” program, and by the German Research Foundation (DFG; GR3946/3−1 and SFB/Transregio 128 A09) to C.C.G.. Monasterium Laboratory supported data analyses and the writing of this manuscript.
Publisher Copyright:
© 2020 Japanese Society for Investigative Dermatology
PY - 2020/11
Y1 - 2020/11
N2 - 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 γδT-cells. AA lesional hair follicles (HFs) overexpress NKG2D and γδTCR activating ligands, e.g. MICA and CD1d, 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 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 Vδ1+T-cells 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. Lesional AA HFs also showed significantly 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.
AB - 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 γδT-cells. AA lesional hair follicles (HFs) overexpress NKG2D and γδTCR activating ligands, e.g. MICA and CD1d, 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 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 Vδ1+T-cells 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. Lesional AA HFs also showed significantly 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.
KW - Alopecia areata
KW - CD200R
KW - CXCL10
KW - CXCL12
KW - Hair follicle
KW - IFNg
KW - NKG2D
KW - gamma deltaT-cells
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U2 - 10.1016/j.jdermsci.2020.09.001
DO - 10.1016/j.jdermsci.2020.09.001
M3 - Article
C2 - 33039243
AN - SCOPUS:85092251142
VL - 100
SP - 129
EP - 138
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
SN - 0923-1811
IS - 2
ER -