MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells

Abstract

Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells. We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts.

Functionally significant metabolic differences between B and T lymphocyte lineages

“…5f). 48 The reduced TE for these mRNAs in resting B-and T-cells could be due to the relatively low baseline mTOR activity in these cells. 47 Replication-associated histones are produced only in the S phase of the cell cycle, though their mRNAs are generated throughout the cell cycle.…”

Macrophage metabolism: a wound‐healing perspective

“…As a master integrator of metabolic signals, mammalian target of rapamycin (mTOR) activity can influence macrophage polarization through the modulation of macrophage metabolism. mTOR is a metabolic sensor that responds to both extracellular immunological signals (such as PRR ligation and cytokines) and intracellular metabolic signals (including nutrient abundance and cellular energy state as determined by the adenine monophosphate (AMP):ATP ratio) to regulate cellular proliferation and growth . mTOR is present in two complexes, mTORC1 and mTORC2, which have distinct structure and function.…”

“…mTOR is a metabolic sensor that responds to both extracellular immunological signals (such as PRR ligation and cytokines) and intracellular metabolic signals (including nutrient abundance and cellular energy state as determined by the adenine monophosphate (AMP):ATP ratio) to regulate cellular proliferation and growth. 54 mTOR is present in two complexes, mTORC1 and mTORC2, which have distinct structure and function. In macrophages, mTORC1 has been shown to either promote or inhibit inflammation in a context-dependent manner.…”

PIKKing a way to regulate inflammation

“…The role of mTOR in innate immunity has been extensively reviewed quite recently [9][10][11] and as such we will only summarize the major roles of mTOR which we believe relate to, or complement the other PIKK family functions. mTOR is the catalytic core of two complexes mTORC1 and mTORC2 which are defined by their accessory proteins.…”