Roles of Hopx in the differentiation and functions of immune cells

Homeodomain only protein (Hopx, HOPX) is a highly evolutionarily conserved, homeodomain-containing, small protein expressed in multiple tissues and cell types, including those of hematopoietic origin. The quasi-ubiquitous presence of Hopx contrasts with its specialized and context-dependent roles in various cell lineages. Recently, versatile functions of Hopx have been revealed in immune cells, including T lymphocytes with effector and regulatory roles. The induction of Hopx expression can indicate early developmental and differentiation pathways, and early Hopx expression characterizes the recently identified pre-effector T cells that become destined for subsequent effector differentiation. Further, specific molecular mechanisms of Hopx are indispensable for the functional homeostasis of peripherally induced regulatory T cells (pTreg cells). Here we offer a perspective on these diverse roles of Hopx in immune cells and discuss the recent advances that helped to clarify the relevant functions and mechanisms of Hopx. •Hopx is a transcription co-factor expressed in various cell types.•Hopx expression marks pre-effector T cells destined for subsequent effector differentiation.•Molecular mechanisms of Hopx regulate homeostasis of peripherally induced regulatory T cells.