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

• Published in: bioRxiv
• Main Authors: Banks, Lauren B, Sklarz, Tammarah, Gohil, Mercy, O'Leary, Claire, Behrens, Edward M, Sun, Hong, Chen, Youhai H, Koretzky, Gary A, Jordan, Martha S
• Format: Journal Article Paper
• Language: English
• Published: United States Cold Spring Harbor Laboratory 10.06.2024
• Edition: 1.1
• Subjects: Immunology; CD4 T cell; MOG; Th2 cells; Akt2; Th17 cells
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2024.06.07.598023

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 under Th2 polarizing conditions. , 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.