The Ubiquitin Ligase Cul5 Regulates CD4 T Cell Fate Choice and Allergic Inflammation

Overview

Journal Nat Commun

Specialty Biology

Date 2022 May 19

PMID 35589717

Authors

Binod Kumar

Natania S Field

Dale D Kim

Asif A Dar

Yanqun Chen

Aishwarya Suresh

Christopher F Pastore

Li-Yin Hung

Nadia Porter

Keisuke Sawada

Palak Shah

Omar Elbulok

Emily K Moser

DeBroski R Herbert

Paula M Oliver

Affiliations

Soon will be listed here.

Abstract

Antigen encounter directs CD4 T cells to differentiate into T helper or regulatory cells. This process focuses the immune response on the invading pathogen and limits tissue damage. Mechanisms that govern T helper cell versus T regulatory cell fate remain poorly understood. Here, we show that the E3 ubiquitin ligase Cul5 determines fate selection in CD4 T cells by regulating IL-4 receptor signaling. Mice lacking Cul5 in T cells develop Th2 and Th9 inflammation and show pathophysiological features of atopic asthma. Following T cell activation, Cul5 forms a complex with CIS and pJak1. Cul5 deletion reduces ubiquitination and subsequent degradation of pJak1, leading to an increase in pJak1 and pSTAT6 levels and reducing the threshold of IL-4 receptor signaling. As a consequence, Cul5 deficient CD4 T cells deviate from Treg to Th9 differentiation in low IL-4 conditions. These data support the notion that Cul5 promotes a tolerogenic T cell fate choice and reduces susceptibility to allergic asthma.

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