POSH Regulates CD4+ T Cell Differentiation and Survival

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• The scaffold molecule POSH (Plenty Of SH3 structures) is known to regulate proliferation and effector function in CD8(+) T cells.
• The specific role of POSH in CD4(+) T cells remains uncharacterized.

Purpose of the Study:

• To investigate the function of the POSH scaffold complex in CD4(+) T cells.
• To compare the mechanisms of POSH regulation in CD4(+) versus CD8(+) T cells.

Main Methods:

• Disruption of the POSH scaffold complex in T cells.
• Transcriptional profiling to assess differentiation skewing.
• Analysis of cell survival and cell cycle entry.
• Investigation of Tak1 and JNK signaling pathways.
• Characterization of POSH scaffold complex composition and posttranslational modifications.

Main Results:

• Disruption of POSH in CD4(+) T cells led to a strong skew toward Th2 differentiation, decreased cell survival, and no effect on cell cycle entry.
• In contrast, POSH in CD8(+) T cells regulates cell cycle and does not impact survival.
• POSH disruption in CD4(+) T cells resulted in loss of Tak1-dependent JNK1/2 activation and Tak1-mediated survival.
• In CD8(+) T cells, POSH regulates JNK1 but not JNK1/2.
• Unique POSH complex composition and posttranslational modifications were observed in CD4(+) and CD8(+) T cells.

Conclusions:

• The regulatory mechanisms of POSH function differ significantly between CD4(+) and CD8(+) T cells.
• POSH is essential for integrating cell-type-specific signals that control T cell differentiation, survival, and function.