Dataset Information

TCR signal–enhancing mutation alters lipid metabolism of thymocytes and impairs antitumor immunity of mature T cells

ABSTRACT: The T cell receptor (TCR), a master regulator of adaptive immunity, serves as a molecular transducer that converts antigen recognition into precisely modulated intracellular signals, orchestrating both T cell development and effector functions. In this study, we leveraged a germline CD3εI173A mutation, a previously characterized alteration that amplifies TCR signaling through the disruption of inhibitory lipid interactions, to dissect how thymocyte-intrinsic TCR signaling amplification influences the fate of mature T cells. Remarkably, thymic double-positive cells in CD3εI173A mice with altered TCR repertoires demonstrated a significant downregulation of the phosphatidylserine decarboxylase homolog gene AC149090.1. This modulation triggered a comprehensive rewiring of lipid metabolic pathways, establishing a systemic compensatory mechanism to counterbalance excessive TCR signaling. These metabolic adaptations culminated in functionally compromised mature T cells, characterized by diminished activation potential, reduced proliferative capacity, and impaired antitumor efficacy in CD3εI173A mice. Our results underscore the critical role of thymic TCR signaling in T cell development for sustaining immune homeostasis and orchestrating mature T cell functionality, unveiling the lipid metabolic plasticity during thymocyte development that acts as a critical regulatory checkpoint for maintaining immune homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE288784 | GEO | 2025/10/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The thymus constitutes the primary lymphoid organ for the majority of T cells. The phosphatidyl-inositol 3 kinase (PI3K) signaling pathway is involved in lymphoid development. Defects in single components of this pathway prevent thymocytes from progressing beyond early T cell developmental stages. Protein kinase B (PKB) is the main effector of the PI3K pathway. To determine whether PKB mediates PI3K signaling in early T cell development, we characterized PKB knockout thymi. Our results reveal a significant thymic hypocellularity in PKBalpha-/- neonates and an accumulation of early thymocyte subsets in PKBalpha-/- adult mice. The latter finding is specifically attributed to the lack of PKBalpha within the lymphoid component of the thymus. Microarray analyses show that the absence of PKBalpha in early thymocyte subsets modifies the expression of genes known to be involved in pre-TCR signaling, in T cell activation, and in the transduction of interferon-mediated signals. This report highlights the specific requirements of PKBalpha for thymic development. Experiment Overall Design: Early thymocyte subsets (DN3 and ISP8) were sorted by FACS from 4 PKBalpha-/- / PKBalpha+/+ mouse littermate pairs. The same number of DN3 or ISP8 cells was sorted (7 000 to 25 000 cells) within a PKBalpha-/- / PKBalpha+/+ pair. Four replicates per condition were then analysed (4xPKBalpha-/- DN3, 4xPKBalpha+/+ DN3, 4xPKBalpha-/- ISP8, 4xPKBalpha+/+ ISP8). Total RNA was extracted using PicoPureTM RNA isolation kit (Arcturus, Sunnyvale, CA, USA) and RNA quality was controlled using the 2100 Bioanalyser (Agilent Technologies, Santa Clara, CA, USA). Total RNA was amplified and labeled using the Affymetrix 2-cycle 3â labelling kit according to manufacturerâs instructions. After fragmentation, 10 ug cRNA was hybridised to mouse genome 430 2.0 GeneChips (Affymetrix, Santa Clara, CA). The supplementary file represents the expression values estimated using the GC-RMA function provided by Refiner 3.1 (Genedata, Basel, Switzerland) for each of the samples.

Dataset Information

TCR signal–enhancing mutation alters lipid metabolism of thymocytes and impairs antitumor immunity of mature T cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets