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PP2A catalytic subunit alpha is critically required for CD8 + T cell homeostasis and anti-bacterial responses.

Xian ZhouMeilu LiMinji AiYanfeng LiXingxing ZhuMichael J HansenJun ZhongKenneth L JohnsonRoman ZenkaAkhilesh PandeyLarry R PeaseHu Zeng
Published in: bioRxiv : the preprint server for biology (2024)
While the functions of tyrosine phosphatases in T cell biology have been extensively studied, our knowledge on the contribution of serine/threonine phosphatases in T cells remains poor. Protein phosphatase 2A (PP2A) is one of the most abundantly expressed serine/threonine phosphatases. It is important in thymocyte development and CD4 + T cell differentiation. Utilizing a genetic model in which its catalytic subunit alpha isoform (PP2A Cα) is deleted in T cells, we investigated its contribution to CD8 + T cell homeostasis and effector functions. Our results demonstrate that T cell intrinsic PP2A Cα is critically required for CD8 + T cell homeostasis in secondary lymphoid organs and intestinal mucosal site. Importantly, PP2A Cα deficient CD8 + T cells exhibit reduced proliferation and survival. CD8 + T cell anti-bacterial response is strictly dependent on PP2A Cα. Expression of Bcl2 transgene rescues CD8 + T cell homeostasis in spleens, but not in intestinal mucosal site, nor does it restore the defective anti-bacterial responses. Finally, proteomics and phosphoproteomics analyses reveal potential targets dependent on PP2A Cα, including mTORC1 and AKT. Thus, PP2A Cα is a key modulator of CD8 + T cell homeostasis and effector functions.
Keyphrases
  • protein kinase
  • signaling pathway
  • healthcare
  • regulatory t cells
  • poor prognosis
  • dendritic cells
  • gene expression
  • cell proliferation
  • long non coding rna
  • immune response
  • protein protein
  • small molecule
  • free survival