P5.53 Comparative immunophenotypology of the human hair and nail apparatus

Taisuke Ito^*†, Natsuho Ito*, Matthias Saathoff*, Albrecht Bettermann*, Masahiro Takigawa†, Brian J. Nickoloff**, Ralf Paus*

*Department of Dermatology, University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany, †Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan, **Department of Pathology, Loyola University of Chicago Medical Center, Chicago, Illinoi, U.S.A

Although acute and chronic infections of the nail apparatus (paronychia, onychomycoses) and hair (folliculitis) rank among the more frequently encountered diseases in general clinical practise and dermatology, it is essentially unknown how the nail immune system differs from the skin or hair follicle immune system. Therefore, we have investigated the normal nail immune system in the digits of three human infants by immunohistology, and have compared the immunophenotying (Immunoreactivity: IR) results with human anagen VI hair follicles.

The number of CD4+ and CD8+ T cells in the mesenchyme around the epithelial nail matrix is extremely reduced compared to that in the dermis adjacent proximal nail fold PNF - just as we had previously described for human scalp hair follicles. CD1a+ Langerhans cells (LC) were frequently detected in the epithelium of the proximal nail matrix (PNF) and the distal ORS of the hair follicle. In contrast, they were only very rarely detected in both the nail and hair follicle matrix. Hair and dorsal nail matrix both displayed HLA-DP/DQ/DR negative-LCs. CD68+ macrophages were abundantly distributed throughout the periungual and perifollicular mesenchyme. However, in contrast to macrophages of the follicular connective tissue sheath, macrophages around the nail matrix seem to be functionally impaired because of low or absent HLA-DP/DQ/DR expression. Surprisingly, HLA-A/B/C expression was prominently downregulated on both keratinocytes and melanocytes of the PNM, compared to other regions of the nail epithelium. In contrast, HLA-G, which suppresses NK cell lysis e.g. in the fetotrophoblast and is identified here for the first time in the human nail apparatus, was strongly positive in the PNM. Both nail and hair matrix showed strong IR for locally generated potent immunosuppressants such as TGF-1, -MSH, ACTH and macrophage inhibitory factor (inhibitor of NK cell activity). Interestingly, MICA, which activates NK cell lysis, was strongly expressed in nail and hair matrix. NKG2D (MICA receptor)-positive cells resided just around the nail and hair matrix. This suggests that the nail immune system strikingly differs from the skin immune system, but shows intriguing similarities to the hair follicle immune system, including the establishment of an area of relative immune privilege in the PNM. These findings may help to explain the notorious chronicity and therapy-resistance of nail and hair infections, and encourage a systematic comparative approach in the elucidation of nail and hair immunology.