RhoG’s Role in T Cell Activation and Function

Abstract

The role of RhoG in T cell development is redundant with other Racs subfamily members, and this redundancy may be attributed to redundant signal transduction pathways. However, the absence of RhoG increases TCR signalling and proliferation, implying that RhoG activity is critical during late T cell activation following antigen–receptor interaction. Moreover, RhoG is required to halt signal transduction and prevent hyper-activated T cells. Despite increase in TCR signalling, cell proliferation is inhibited, implying that RhoG induces T cell anergy by promoting the activities of transcription factors, including nuclear factor of activated T cell (NFAT)/AP-1. The role of NFAT plays in T cell anergy is inducing the transcription of anergy-associated genes, such as IL-2, IL-5, and IFN-γ. Although information about RhoG in T cell-related diseases is limited, mutant forms of RhoG, Ala151Ser and Glu171Lys have been observed in thymoma and hemophagocytic lymphohistiocytosis (HLH), respectively. Current information only focuses on these two diseases, and thus the role of RhoG in normal and pathological circumstances should be further investigated. This approach is necessary because RhoG and its associated proteins represent prospective targets for attack particularly in the therapy of cancer and immune-mediated illnesses.

Soluble immune checkpoint factors reflect exhaustion of antitumor immunity and response to PD-1 blockade

“…With the exception of sCTLA-4, the number of correlated genes was sufficient for pathway analysis ( Figure 6B ). The enriched pathways for genes whose expression was positively correlated with sPD-L1 concentration included those related to cell proliferation and immune activation, whereas enriched pathways for genes correlated with sPD-1 level included those related to immune responses, T cell activation, and T cell anergy (signaling by Rho GTPases; Figure 6B ) ( 45 ). Examination of genes characteristic of naive, progenitor exhausted, or terminally exhausted T cells ( 46 ) revealed that the concentration of each soluble immune factor was highly correlated with the expression of genes associated with terminally exhausted T cells, but not with that of those associated with naive or progenitor exhausted phenotypes ( Figure 6C and Supplemental Table 4 ).…”

A prognostic model for anoikis-related genes in pancreatic cancer

“…ROGH is a member of the RHO family of small GTPases, playing a crucial role in regulating the equilibrium of T-cells.RhoG plays a part in the internalization of TCR at the immunological synapse (IS), a process crucial for effective T-cell activation. However, the current knowledge about this process is still insufficient 44 , CDK11A belongs to a group of protein kinases that encode serine/threonine proteins and are cleaved by cysteine asparaginase. It is suggested that CDK11A may be involved in the process of apoptosis.…”

Role of Rho GTPases in inflammatory bowel disease

“…Cdc42 deficiency results in the overactivation of murine T cells [ 98 ]. Moreover, RhoG and RhoH have been reported to regulate the TCR signaling pathway, mainly as the suppressor and enhancer, respectively [ 86 , 99 ].…”