Year: 2025
Type: article
Abstract: Description T cell fate decisions are guided by complex signaling networks that depend on the cell’s developmental and differentiation state. Building on our previous work with POSH inhibitors in vitro, we generated T cell-specific POSH knockout (KO) mouse models (B6 and OT-I TCR CD4-Cre/POSHfl/fl/GFP and GranzymeB-Cre/POSHfl/fl/GFP). In this study, we investigated the role of the scaffold protein Plenty of SH3 domains (POSH) in regulating T cell fate decisions. Loss of POSH resulted in a significant reduction in mature peripheral CD25+ CD4 and CD8 T cells. In the thymus, POSH deletion led to reduced thymic cellularity. Notably, in CD8 T cells from CD4-Cre/POSHfl/fl/GFP mice, POSH deletion caused delayed thymocyte maturation, including the transition through the SM, M1, and M2 single-positive (SP) stages. To assess POSH’s role in immune responses, OT-I T cells were adoptively transferred into hosts and challenged with VSV-OVA infection. POSH-deficient OT-I cells exhibited defects in proliferation and survival during the contraction phase, impairing memory formation. However, homeostatic proliferation was unaffected by the loss of POSH. These findings highlight the role of POSH in regulating T cell fate decisions and suggest potential therapeutic avenues for manipulating T cell-mediated immunity in disease settings. Funding Sources NIH/NIBIB EB026560, American Cancer Society, MU-MITC Pilot Program, MU-SOM Bridge Funding Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)
Source: The Journal of Immunology
Institution: University of Missouri
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416446505
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