Myeloid cells are fundamental players in the regulation of tissue homeostasis and immune responses. These cells undergo large metabolic shifts as they transition between resting and activated states and the tuning of cellular metabolism upon alteration in nutrient levels and oxygen tension is important to retain function. This has led to the establishment of the field of Immunometabolism.
Generally, myeloid cells characterized by the production of proinflammatory mediators, microbicidal activity, and release of reactive oxygen species (ROS), utilize glycolysis and assume classical or “M1” phenotype, whereas “alternative” activated or “M2”, rely on oxidative phosphorylation (OXPHOS) and mediate healing, humoral responses, and tumor progression. While in vitro-derived cultures like Bone Marrow-Derived Macrophages (BMDMs) have been routinely used to study myeloid cell functions, resident cells and cells recruited in response to stimuli have different origins and are both at the front line of defense. Little is known about immune resident cell metabolism, or which fuels are available in tissue niches that govern cell function. The availability of local fuels and the restricted tissue localization of certain metabolites could be linked to and required for myeloid cell metabolic processes that sustain their function in distinct contexts.
Past research revealed that leucocyte functions correlate with glutamine availability. Resident myeloid cells in the peritoneal cavity indeed have the innate ability to use glutamine, but do not fully endorse it in homeostasis but rather during stress and challenge. In other niches like lung or adipose tissue, the abundance of specific lipid species respectively dictates the function of resident myeloid cells that acquire transcriptional signatures dominated by genes associated with lipid metabolism; change in conditions of the niche in pathological assets, with the presence of infiltrating recruited cells drives major diversions of metabolic utilization of fuels. In the context of tumors, factors imposed by the tumor microenvironment, including metabolic contexts and cytokine milieus, shape the composition of immune infiltrates, but myeloid cells themselves can also alter local metabolite levels potentially contributing to suppressive environments. Understanding these components is critical to target myeloid response to cancer and inflammation by leveraging their metabolic plasticity and therapeutically manipulate the metabolites within niches.
The goal of this research will be the examination of myeloid cell metabolic requirements with consideration of the corresponding tissue-niche environment. New technologies allow research towards this goal with unprecedented resolution and accuracy. Advances in microscopy platforms, CRISPR gene-editing tools, single-cell next-generation, high-resolution mass spectrometry for metabolomics, carbon tracing and lipidomics, and novel approaches in spatially resolved metabolic imaging enable precise metabolic and anatomical characterizations of niches and knowledge of gene regulatory mechanisms governing cell behaviors.
We welcome submissions of Original Research, Reviews, Mini Reviews, and Perspectives covering, but not limited to, the following sub-topics:
• Metabolic differences in distinct microenvironments
• Carbon source requirements for myeloid cell function in tissues
• Biochemical sufficiencies for myeloid development and differentiation in unique tissue-niches
• Metabolic crosstalk between myeloid cells and niche interstitial cells and tumor cells
• Energetics control of tissue-linked transcriptional and epigenetic events in myeloid cells
• High-resolution technologies at the service of myeloid cell biology
Disclaimer: Dr. Palmieri is serving in her personal capacity. The views expressed are her own and do not necessarily represent the views of the National Institutes of Health or the United States Government.
Myeloid cells are fundamental players in the regulation of tissue homeostasis and immune responses. These cells undergo large metabolic shifts as they transition between resting and activated states and the tuning of cellular metabolism upon alteration in nutrient levels and oxygen tension is important to retain function. This has led to the establishment of the field of Immunometabolism.
Generally, myeloid cells characterized by the production of proinflammatory mediators, microbicidal activity, and release of reactive oxygen species (ROS), utilize glycolysis and assume classical or “M1” phenotype, whereas “alternative” activated or “M2”, rely on oxidative phosphorylation (OXPHOS) and mediate healing, humoral responses, and tumor progression. While in vitro-derived cultures like Bone Marrow-Derived Macrophages (BMDMs) have been routinely used to study myeloid cell functions, resident cells and cells recruited in response to stimuli have different origins and are both at the front line of defense. Little is known about immune resident cell metabolism, or which fuels are available in tissue niches that govern cell function. The availability of local fuels and the restricted tissue localization of certain metabolites could be linked to and required for myeloid cell metabolic processes that sustain their function in distinct contexts.
Past research revealed that leucocyte functions correlate with glutamine availability. Resident myeloid cells in the peritoneal cavity indeed have the innate ability to use glutamine, but do not fully endorse it in homeostasis but rather during stress and challenge. In other niches like lung or adipose tissue, the abundance of specific lipid species respectively dictates the function of resident myeloid cells that acquire transcriptional signatures dominated by genes associated with lipid metabolism; change in conditions of the niche in pathological assets, with the presence of infiltrating recruited cells drives major diversions of metabolic utilization of fuels. In the context of tumors, factors imposed by the tumor microenvironment, including metabolic contexts and cytokine milieus, shape the composition of immune infiltrates, but myeloid cells themselves can also alter local metabolite levels potentially contributing to suppressive environments. Understanding these components is critical to target myeloid response to cancer and inflammation by leveraging their metabolic plasticity and therapeutically manipulate the metabolites within niches.
The goal of this research will be the examination of myeloid cell metabolic requirements with consideration of the corresponding tissue-niche environment. New technologies allow research towards this goal with unprecedented resolution and accuracy. Advances in microscopy platforms, CRISPR gene-editing tools, single-cell next-generation, high-resolution mass spectrometry for metabolomics, carbon tracing and lipidomics, and novel approaches in spatially resolved metabolic imaging enable precise metabolic and anatomical characterizations of niches and knowledge of gene regulatory mechanisms governing cell behaviors.
We welcome submissions of Original Research, Reviews, Mini Reviews, and Perspectives covering, but not limited to, the following sub-topics:
• Metabolic differences in distinct microenvironments
• Carbon source requirements for myeloid cell function in tissues
• Biochemical sufficiencies for myeloid development and differentiation in unique tissue-niches
• Metabolic crosstalk between myeloid cells and niche interstitial cells and tumor cells
• Energetics control of tissue-linked transcriptional and epigenetic events in myeloid cells
• High-resolution technologies at the service of myeloid cell biology
Disclaimer: Dr. Palmieri is serving in her personal capacity. The views expressed are her own and do not necessarily represent the views of the National Institutes of Health or the United States Government.