JCI Insights, Billi et al 2019

We recently identified VGLL3, a putative transcription factor enriched in skin of women, as a hormone-independent regulator of female-biased genes involved in autoimmunity, including factors with established roles in lupus pathogenesis. However, the local and systemic consequences of VGLL3 enrichment in female skin are unknown. Here we study skin-targeted overexpression of Vgll3 in a mouse model. To interrogate the immune landscape, we analyzed skin-draining lymph nodes, spleen, and ear tissue from WT and transgenic mice with mass cytometry (CyTOF) using a 37-parameter panel. Conclusion: CyTOF data showed B cells were overrepresented among inflammatory cells in transgenic lymph nodes, with a similar although less pronounced trend in spleen. It was also found that neutrophils were enriched in transgenic ear samples. Together, these findings indicate that Vgll3 overexpression in the epidermis drives a systemic inflammatory response with B cell expansion that extends beyond the skin to the lymphatic system. Panel staining was validated on wild-type mouse spleens. Data are representative of two independent experiments