The role of CNS1 in shaping the CD4+ T cell and Treg response to influenza

Recently, the field has gained critical insights into Tregs in ALI, and the diversity of gene expression and function of Tregs throughout ALI is beginning to be described. However, the origins of these Tregs has remained unknown.

Here, we utilized a mouse model lacking the conserved noncoding sequence 1 (CNS1) of the Foxp3 promoter, which results in attenuated peripheral Treg induction, to understand the role(s) of peripheral Tregs in the initiation, pathogenesis, and recovery from acute lung injury. We found that CNS1-deficient mice exhibit more severe ALI and delayed resolution. We find that CNS1 may have roles in shaping the T cell response during influenza and that CNS1-deficient Tregs have several cell-intrinsic maladaptive phenotypes, overall giving us insight into the Treg plasticity that may aid in ALI recovery.