MiR-21 sustains CD28 signalling and low-affinity T-cell responses at the expense of self-tolerance.

ABSTRACT:

Objective

miR-21 is highly expressed in iNKT and activated T cells, but its T-cell autonomous functions are poorly defined. We sought to investigate the role of miR-21 in the development and functions of T and iNKT cells, representing adaptive and innate-like populations, respectively.

Methods

We studied mice with a conditional deletion of miR-21 in all mature T lymphocytes.

Results

Thymic and peripheral T and iNKT compartments were normal in miR-21 KO mice. Upon activation in vitro, miR-21 depletion reduced T-cell survival, T_H17 polarisation and, remarkably, T- and iNKT cell ability to respond to low-affinity antigens, without altering their response to high-affinity ones. Mechanistically, miR-21 sustained CD28-dependent costimulation pathways requi

SUBMITTER: Fedeli M 

PROVIDER: S-EPMC8454917 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature