Thread by @JIDJournals

Talk #3 in Plenary III - "Involucrin Deficiency results in Decreased Vitamin D Receptor‐Mediated Inflammation and Csnk1e Isoform Bias" from the lab of @cdgstrong21 at @WashUDerm #sid2021 1/n

Involucrin is a major scaffolding protein in the epidermis, and the @cdgstrong21 lab recently discovered that there is a positive selection pressure for increased involucrin expression out-of-Africa - this is work that is in press @sid2021 2/n

Interesting that involucrin knockout mice develop a normal skin barrier - but the role of involucrin for skin homeostasis is not known. To determine the response, a well known vitD agonist model of cutaneous inflammation was applied to involucrin knockout mice #sid2021 3/n

drumroll... involucrin knockout mice develop less ear thickness in response to vitD agonist, what can explain this reduced inflammatory response? CD4+ T cells and TSLP receptor expression was reduced in the involucrin knockouts, explaining the reduced response #sid2021 4/n

Digging in deeper, they sought to determine if involucrin knockout mice had differentially accessible chromatin regions (by ATAC-seq), differentially expressed genes (by RNA-seq) or differentially expressed proteins (by LC/MS). 5/n #SID2021

Csnk1e (Casein Kinase 1), a gene related to circadian rhythms, was found to have differentially accessible chromatin regions and differentially (lower) expressed levels of protein. 6/n #sid2021

Bringing back to human evolution - they show that as skin pigmentation increases, involucrin and vitamin D receptor expression both decreases by similar amounts. There appears to be a conserved dosage relationship between these two. 7/n #SID2021

A question after the talk - what is the role of circadian rhythm in the skin? @cdgstrong21 lab's hypothesis is that variation in involucrin and csnk1 levels may reflect longer vs shorter duration circadian rhythms at different latitudes, but more study is needed! 8/8 #sid2021