014 C1ORF162 is specifically expressed by pathogenic Th2 cells in atopic dermatitis

Abstract

Pathogenic Th2 cells are a recently described subpopulation of allergen-specific Th2 cells that are crucial mediators of type 2 immune diseases such as asthma and allergic dermatitis. Understanding the unique biology of pathogenic Th2 cells holds the promise of identifying specific and novel therapeutic targets. The gene chromosome 1 open reading frame 162 (C1ORF162) has been repeatedly identified to be specifically expressed by pathogenic Th2 cells and its expression correlates with disease severity in atopic dermatitis. Yet, its function is completely unknown. Here, we characterized the cellular expression of C1ORF162 at the mRNA and protein level in primary human T cells. RNA sequencing and qPCR analysis confirmed that both in-vivo- and in-vitro- primed Th2 express higher levels of C1ORF162 than Th1 and Th17 cells. In addition, C1ORF162 expression in Th2 cells correlated with the expression of cytokines that are specifically expressed by pathogenic Th2 cells, such as IL-9 and IL-5. These findings were confirmed at the protein level by Western Blot and FACS analysis. Initial protein localization experiments and functional analyses suggest that C1ORF162 is a perinuclear protein that is rapidly downregulated by IL-2 signaling. Finally, C1ORF162 was found to be expressed by T cells infiltrating lesional skin of atopic dermatitis. In conclusion, C1ORF162 is consistently expressed in pathogenic Th2 cells and associated with disease severity in atopic dermatitis. Future experiments aim to further define the identity and function of C1ORF162 in human Th2 cells. Based on the close association of C1ORF162 with pathogenic Th2 cells, these studies may have therapeutic implications for type 2-driven disease in the skin and beyond.