Butyrophilin-like 2 (BTNL2) to the Rescue: controlling autoaggressive dermal gamma delta (GD) T lymphocytes in human hair follicles (HFs) 3747

Abstract Description Butyrophilin-like 2 (BTNL2), a member of the immunoglobulin (Ig) superfamily, regulates immune responses and maintains immune tolerance. Yet, it remains largely unknown how BTNL2 interacts with gamma/delta (GDT) T cells, key immune surveillance cells in epithelial tissues. Since GDT cells have recently surfaced as important pathogenic T cells in alopecia areata (AA), which results from collapse of the hair follicle’s (HF) physiological immune privilege (IP), we have asked here how BTNL2 influences HF interactions with GDT cells. By immunofluorescent microscopy, we found BTNL2 to be predominately expressed in the outer root sheath keratinocytes of healthy human scalp HFs. Human scalp skin VD1 GDT and CD8 T cells were co-cultured with autologous stressed and non-stressed HFs ex vivo. BTNL2 expression was significantly lower in stressed than in non-stressed HFs (p < 0.01), correlating with increased expression of NKG2D and IFNg in VD1 GDT (p < 0.05) (stressed HFs overexpress MICA and CD1d). In stressed HFs, cytotoxicity by VD1 GDT and CD8+ T cells was heightened, leading to HF dystrophy, as indicated by melanin clumping and premature catagen induction—hallmarks of AA-like immune-mediated HF damage. Interrogating immune-privileged HFs as an instructive model mini-organ, our study introduces BTNL2 expression on HF keratinocytes as a novel player in controlling autoaggressive dermal GDT cell responses in human skin and as a novel candidate target in future AA management. Funding Sources Team Science Funding Program, University of Miami Topic Categories Mucosal and Regional Immunology (MUC)