Title

Autoimmune diabetes is regulated by the vanilloid receptor 1 ligand capsaicin

Date of Completion

January 2011

Keywords

Health Sciences, Immunology

Degree

Ph.D.

Abstract

Vanilloid receptor 1 (VR1) is expressed on immune cells as well as on sensory neurons. Here we report that VR1 can regulate immunological events in the gut in response to its ligand capsaicin (CP), a nutritional factor and the pungent component of chili peppers. Orally administered CP attenuates the proliferation and activation of auto-reactive T cells in pancreatic lymph nodes (PLN) and protects mice from development of type 1 diabetes (T1D). Engagement of VR1 enhances a discreet population of CD11b+/F4/80 + macrophages that express anti-inflammatory factors such as IL-10 and PD-L1. This macrophage population is essential for CP mediated attenuation of T cell proliferation. VR1 expression is required for CP to inhibit proliferation of auto-reactive T cells. The protective effect is partially restored in (VR1 +/+→VR1−/− bone marrow (BM) chimeric mice, implying that the role of VR1 may involve crosstalk between neuronal and immunological systems in vivo. Furthermore, engagement of VR1 enhances a population of Tr1-like cells in the PLN which may be able to protect naïve NOD from onset of T1D upon adoptive transfer. These findings suggest that exogenous and perhaps endogenous ligands of VR1 can have profound effects on the development of gut mediated immune tolerance and autoimmunity by directly influencing the immune system. ^