Isoform‐specific functions of Ras in T‐cell development and differentiation

• Published in: European journal of immunology 2023-07, Vol.53 (7), p.e2350430-n/a
• Main Authors: Bodhale, Neelam, Nair, Arathi, Saha, Bhaskar
• Format: Article
• Language: English
• Subjects: Apoptosis; Autoimmune Diseases; Autoimmunity; Cell activation; Cell Differentiation; Cell proliferation; Homeostasis; Humans; Immune system; Isoforms; Lymphocytes; Lymphocytes T; Protein Isoforms - genetics; Protein Isoforms - metabolism; Ras isoforms; Receptors, Antigen, T-Cell; Signal Transduction; T cell receptors; T-Lymphocytes; Tumorigenesis; T‐cell differentiation; T‐cell selection; T‐reg differentiation
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.202350430

Ras GTPases, well characterized for their role in oncogenesis, are the cells’ molecular switches that signal to maintain immune homeostasis through cellular development, proliferation, differentiation, survival, and apoptosis. In the immune system, T cells are the central players that cause autoimmunity if dysregulated. Antigen‐specific T‐cell receptor (TCR) stimulation activates Ras‐isoforms, which exhibit isoform‐specific activator and effector requirements, functional specificities, and a selective role in T‐cell development and differentiation. Recent studies show the role of Ras in T‐cell‐mediated autoimmune diseases; however, there is a scarcity of knowledge about the role of Ras in T‐cell development and differentiation. To date, limited studies have demonstrated Ras activation in response to positive and negative selection signals and Ras isoform‐specific signaling, including subcellular signaling, in immune cells. The knowledge of isoform‐specific functions of Ras in T cells is essential, but still inadequate to develop the T‐cell‐targeted Ras isoform‐specific treatment strategies for the diseases caused by altered Ras‐isoform expression and activation in T cells. In this review, we discuss the role of Ras in T‐cell development and differentiation, critically analyzing the isoform‐specific functions. As recent studies show the role of Ras in T‐cell‐mediated autoimmunity, herein, we review the role of Ras in T‐cell development and differentiation. We have critically analyzed and have provided new insights into the Ras isoform‐specific functions in the phases of the T‐cell development.