Cell-intrinsic mechanisms to restrain inflammatory responses in T lymphocytes.

ABSTRACT

A mechanistic understanding of the regulatory circuits that control the effector responses of memory T helper lymphocytes, and in particular their ability to produce pro-inflammatory cytokines, may lead to effective therapeutic interventions in all immune-related diseases. Activation of T lymphocytes induces robust immune responses that in most cases lead to the complete eradication of invading pathogens or tumor cells. At the same time, however, such responses must be both highly controlled in magnitude and limited in time to avoid unnecessary damage. To achieve such sophisticated level of control, T lymphocytes have at their disposal an array of transcriptional and post-transcriptional regulatory mechanisms that ensure the acquisition of a phenotype that is tailored to the incoming stimulus while restraining unwarranted activation, eventually leading to the resolution of the inflammatory response. Here, we will discuss some of these cell-intrinsic mechanisms that control T cell responses and involve transcription factors, microRNAs, and RNA-binding proteins. We will also explore how the same mechanisms can be involved both in anti-tumor responses and in autoimmunity.