Dermot Kelleher

Immune surveillance and adaptive immune responses, involving continuously circulating and tissue-resident T-lymphocytes, provide host defense against infectious agents and possible malignant transformation while avoiding autoimmune tissue damage. Activation, migration, and deployment of T-cells to affected tissue sites are crucial for mounting an adaptive immune response. An effective adaptive immune defense depends on the ability of T-cells to dynamically reprogram their metabolic requirements in response to environmental cues. Inability of the T-cells to adapt to specific metabolic demands may skew cells to become either hyporesponsive (creating immunocompromised conditions) or hyperactive (causing autoimmune tissue destruction). Here, we review maladaptive T-cell metabolic fitness that can cause autoimmune diseases and discuss how T-cell metabolic programs can potentially be modulated to achieve therapeutic benefits.

Immune surveillance and adaptive immune responses, involving continuously circulating and tissue-resident T-lymphocytes, provide host defense against infectious agents and possible malignant transformation while avoiding autoimmune tissue damage. Activation, migration, and deployment of T-cells to affected tissue sites are crucial for mounting an adaptive immune response. An effective adaptive immune defense depends on the ability of T-cells to dynamically reprogram their metabolic requirements in response to environmental cues. Inability of the T-cells to adapt to specific metabolic demands may skew cells to become either hyporesponsive creating immunocompromised conditions or hyperactive causing autoimmune tissue destruction. Here, we review maladaptive T-cell metabolic fitness that can cause autoimmune diseases and discuss how T-cell metabolic programs can potentially be modulated to achieve therapeutic benefits.

Editorial: Adaptor Protein Regulation in Immune Signalling

The α_Lβ₂ integrin LFA-1 is known to play a key role in T lymphocyte migration, which is necessary to mount a local immune response, and is also the main driver of autoimmune diseases. This migration-triggering signaling process in T cells is tightly regulated to permit an immune response that is appropriate to the local trigger, as well as to prevent deleterious tissue-damaging bystander effects. Emerging evidence shows that, in addition to prompting a diverse range of downstream signaling cascades, LFA-1 stimulation in T lymphocytes modulates gene-transcription programs, including genetic signatures of TGF-β and Notch pathways, with multifactorial biological outcomes. This review highlights recent findings and discusses molecular mechanisms by which LFA-1 signaling influence T lymphocyte differentiation into the effector subsets Th1, Th17, and induced regulatory T cells. We argue that LFA-1 contact with a cognate ligand, such as ICAM-1, independent of the immune synapse activates a late divergence in T cells’ effector phenotypes, hence fine-tuning their functioning.