035 Biogeographical differences in gene segment usage

Biogeography is known to shape the human skin metagenome, which in turn, helps to shape the adaptive immune system. Clearly, immune-mediated diseases (e.g. hidradenitis, lichen planus, atopic dermatitis, psoriasis, palmoplantar psoriasis/pustulosis) have predilections for specific anatomical sites (axillae, groin, and inguinal folds; dorsal hands, volar wrists, anterior lower legs and oral mucosa; antecubital fossa and popliteal fossa; elbows and knees; and palms and soles; respectively). A better understanding of how immune composition and function differs by anatomic location remains a major gap in our understanding of skin immunology. As a first step to investigate anatomical-specificity of the cutaneous immune response in humans, we have employed our in-house developed bioinformatics pipeline, TCRminer, to characterize intra-person differential TCR gene usage by body site. This analysis revealed differential expression of several TCR gene segments. Specifically, TRAV8-5 was overexpressed in hip skin in comparison to peripheral blood (FDR = 1.97e-35), a finding that was independent of HLA haplotype. The TCR repertoire of the blood was also found to be more diverse than that of the hip. The skin-resident repertoire of the palm was also compared to that of the hip. Results revealed that TRAJ39 was overexpressed (relative fold change = 2.74, FDR = 6.39e-03) in palmar skin, a finding that was independent of HLA haplotype. Palm skin also had significantly less T cell repertoire diversity. Analysis of BCR genes revealed that IgHA1 was poorly expressed in the palm when compared to the hip (relative fold change = 0.06, FDR = 2.02e-05). These findings are relevant because diseases such as palmoplantar psoriasis, hand dermatitis, and palmoplantar pustulosis have a predilection for palmar skin, which according to these results has differential expression of both TCR and BCR receptors.