Th17 specific tissue dynamics in psoriasis 2633

Abstract Description Psoriasis is a chronic autoimmune disorder with broad and often unappreciated health impacts. Classically, psoriasis patients present erythema, thickening, and scaling of the skin. Increased risk of other co-morbidities including psoriatic arthritis indicates a critical need to understand the etiology of psoriasis. Th17 cells are critical players in disease immunopathogenesis, but the exact location, migratory mechanism, and cellular interaction partners are still unknown. Previous work in the lab has shown that Th1 and Th2 utilize unique migratory machinery to navigate different inflamed environments. Since Th1 and Th17 are both found in psoriasis, we sought to determine if these cell types have distinct positioning or mechanisms to interface with the psoriatic microenvironment using the imiquimod (IMQ) mouse model. We identified structural differences in IMQ ECM arrangement using intravital microscopy indicating that Th1 and Th17 motility may need to adapt to this unique landscape. Additionally, we identified Kindlin-1, a regulator of integrin and cytokine signaling, as uniquely upregulated in Th17s suggesting they may be programmed for distinct migration in the psoriatic microenvironment. Future experiments will follow the effect of modulating different integrins or their downstream signals to determine if Th17 has a unique motility mechanism. These studies aim to gain insight into potential new therapeutics by identifying unknown Th17 positional cues in Psoriasis. Funding Sources Supported by NIH PO1AI102851; MERIT R37AI072690 Topic Categories Basic Autoimmunity (BA)