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Akt2 deficiency impairs Th17 differentiation, augments Th2 differentiation, and alters the peripheral response to immunization.

Lauren B BanksTammarah SklarzMercy GohilClaire O'LearyEdward M BehrensHong SunYouhai H ChenGary A KoretzkyMartha S Jordan
Published in: bioRxiv : the preprint server for biology (2024)
Akt1 and Akt2, isoforms of the serine threonine kinase Akt, are essential for T cell development. However, their role in peripheral T cell differentiation remains undefined. Using mice with germline deletions of either Akt1 or Akt2, we found that both isoforms are important for Th17 differentiation, although Akt2 loss had a greater impact than loss of Akt1. In contrast to defective IL-17 production, Akt2 -/- T cells exhibited enhanced IL-4 production in vitro under Th2 polarizing conditions. In vivo , Akt2 -/- mice displayed significantly diminished IL-17A and GM-CSF production following immunization with myelin oligodendrocyte glycoprotein (MOG). This dampened response was associated with further alterations in Th cell differentiation including decreased IFNγ production but preserved IL-4 production, and preferential expansion of regulatory T cells compared to non-regulatory CD4 T cells. Taken together, we identify Akt2 as an important signaling molecule in regulating peripheral CD4 T cell responses.
Keyphrases
  • signaling pathway
  • cell proliferation
  • regulatory t cells
  • dendritic cells
  • type diabetes
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  • adipose tissue
  • protein kinase