Crucial protein enables immune system memory

Confirmation of POSH deletion in POSHfl/fl CD4-Cre mice. (A) Schematic depicting the original SH3rf1tm1a(EUCOMM)Hmgu genetic construct (top) and the construct after deletion of the luciferase/neo cassette (bottom) for the POSHfl/fl gene (B, C) GFP positive T cells were isolated, lysed, and mRNA and protein were isolated. (B) Deletion of exon 7 from the POSH mRNA was confirmed by RTPCR. (POSH mRNA with exon 7–500 bp, Δexon7 POSH mRNA – 300 bp) (C) Deletion of POSH at the protein level was confirmed by western blot. Credit: Frontiers in Immunology (2025). DOI: 10.3389/fimmu.2025.1630599

Researchers at the University of Missouri School of Medicine have recently found that a certain protein may have a large influence on how the immune system functions.

POSH, a structural protein, plays a crucial role in signaling T cells from the immune system and directing them toward the correct infected cells to attack. During an immune response, T cells must mature and specialize to fight a specific infection. Without POSH, however, these cells usually don’t survive long enough to complete that process.

The findings are published in the journal Frontiers in Immunology.

“What we see in our models, the mice who have POSH deleted aren’t able to fight off infections as well,” said study author Mark Daniels. “In addition, when fighting tumor growth, the immune cells can’t replenish themselves as fast as the cancer cells do.”

Since the cells don’t survive long enough, they also don’t become long-term memory cells, which “remember” previous infections. If the body is reinfected, a memory cell can recognize the infection and launch a robust counterattack, often killing the infection before the person experiences any real symptoms.

“Without POSH, the immune system is still able to initially respond, but it’s unable to provide long-term immunity and protection, according to our models,” Daniels said. “Targeting this protein in therapeutic treatments could benefit patients with autoimmune diseases or blood disorders.”

It may also benefit patients diagnosed with cancers involving T cells, like leukemia or lymphoma. Targeting the POSH protein in cancerous cells could help weaken the disease, or it could be useless—depending on the type of cancer and how it formed in the body.

“We have done some research on what types of cancers and tumors would be susceptible to POSH deletion and what wouldn’t, but we need to conduct far more research to figure out what specific cancers could be targeted,” Daniels explained.

One unique feature of the research is that the mice models were developed in-house at the University of Missouri, with help from an international consortium focused on mapping genetic code. Daniels’s team is currently the only one in the world using these models and hopes they can help move other people’s research forward.

More information:
Caitlyn Guldenpfennig et al, The POSH scaffold protein is essential for signal coordination leading to CD8 T cell differentiation and survival, Frontiers in Immunology (2025). DOI: 10.3389/fimmu.2025.1630599

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Crucial protein enables immune system memory (2025, October 16)
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