Calcitonin gene-related peptide (CGRP) may award relative protection from interferon-?-induced collapse of human hair follicle immune privilege

Interferon-? (IFN?)-induced collapse of hair follicle (HF) immune privilege (IP) is a key element in the pathogenesis of alopecia areata. In this pilot study, we investigated whether the immunosuppressive neuropeptide, calcitonin gene-related peptide (CGRP), can protect from and/or restore IFN?-induced HF-IP collapse. After showing that human scalp HFs express CGRP receptor-like receptor (CRLR) immunoreactivity, anagen HFs were cultured in the presence of IFN?, with CGRP added before or after. Adding CGRP after IFN? administration (restoration assay) failed to downregulate IFN?-induced ectopic MHC class I expression, while MHC class II expression was reduced. However, administering CGRP before IFN? application (protection assay) significantly reduced the IFN?-induced overexpression and ectopic expression of MHC class I and II and reduced the increased degranulation of perifollicular mast cells induced by IFN?. This suggests that CGRP may not restore HF-IP once it has collapsed, but may protect it from collapsing. Therefore, CRLR stimulation might help to retard AA progression.