Immune Cell - Adipocyte Crosstalk

We have uncovered a new cAMP-dependent pathway in dendritic cells that controls T helper cell differentiation into the Th17 and Th2 lineages. We showed that cAMP-PKA-CREB signaling reprograms conventional type-2 Dendritic Cells (cDC2s) via repression of transcription factors IRF4 and KLF4 that are essential for cDC2-mediated Th2 induction.  In the lung, deletion of Gnas in CD11c+ dendritic cells in mice leads to spontaneous allergic asthma in response to common aeroallergens such as house dust mites.  In adipose tissue, deletion of Gnas in CD11c+ cells leads to increased lipolysis and adipose tissue wasting. The KO mice are resistant to diet-induced obesity yet consume the same calories.  The mice do not develop hepatic steatosis, are insulin sensitive, consume more oxygen, and have slightly higher body temperature. We are currently investigating how immune cells interact with adipocytes to control energy storage and utilization and protect from obesity.