Transgelin‐2 in immunity: Its implication in cell therapy

Transgelin‐2 is a small 22‐kDa actin‐binding protein implicated in actin dynamics, which stabilizes actin structures and participates in actin‐associated signaling pathways. Much curiosity regarding transgelin‐2 has centered around its dysregulation in tumor development and associated diseases. However, recent studies have shed new light on the functions of transgelin‐2, the only transgelin family member present in leukocytes, in the context of various immune responses. In this review, we outlined the biochemical properties of transgelin‐2 and its physiological functions in T cells, B cells, and macrophages. Transgelin‐2 regulates T cell activation by stabilizing the actin cytoskeleton at the immunological synapse. Transgelin‐2 in B cells also participates in the stabilization of T cell–B cell conjugates. While transgelin‐2 is expressed at trace levels in macrophages, its expression is highly upregulated upon lipopolysaccharide stimulation and plays an essential role in macrophage phagocytosis. Since transgelin‐2 increases T cell adhesion to target cells via boosting the "inside‐out" costimulatory activation of leukocyte function‐associated antigen 1, transgelin‐2 could be a suitable candidate to potentiate the antitumor response of cytotoxic T cells by compensating for the lack of costimulation in tumor microenvironment. We discussed the feasibility of using native or engineered transgelin‐2 as a synergistic molecule in cell‐based immunotherapies, without inducing off‐target disturbance in actin dynamics in other cells. Transgelin‐2, the only transgelin family member present in leukocytes, stabilizes actin structures and actively involves in the context of various immune responses.