004 Calcitonin gene-related peptide (CGRP) acts on endothelial cells (ECs) at a site not in skin to favor th17-type immunity

The neuropeptide CGRP can influence the outcome of in vitro antigen presentation through actions on ECs acting as bystanders. To examine this pathway vivo, we used an inducible, conditional knockout (KO) mouse with RAMP1 (part receptor) deleted ECs. Upon skin immunization dinitrofluorobenzene (DNFB), stimulated CD4+ T cells from draining lymph nodes (LNs) had significantly reduced IL-17A expression increased IFNγ and IL-22 at protein mRNA levels compared to control floxed, Cre- mice (Cre-). determine locus relevant targeted by CGRP, wild-type (WT) was grafted onto KO mice. Mice were immunized DNFB 7 wk later grafts. Draining LNs harvested 3 d later, isolated anti-CD3 anti-CD28 monoclonal Abs. Supernatants 48-hr cytokine content determined ELISA. With WT skin, there a trend production statistical significance only for IL-22. When similarly given grafts, no significant differences seen. However, genetic analyses grafts found both donor host cells, perhaps explaining uncertain results. So, second type experiment performed. grafted, above, painted 1-hr before being put recipients. procedure, vascular lymphatic channels are not yet present, but cell is likely greatly reduced. mice, less IL-17A, more toward LN seen These data suggest that skin. In regard, it may be expected taking place regional nodes.