Studying the metabolism and function of myeloid dendritic cells and neutrophils in distinct tissues in health and aging

Introduction

Myeloid cells, such as dendritic cells (DCs) and neutrophils, reside in various organs to respond to insults and are key to controlling immunity and inflammation. However, their aberrant activities in the elderly can cause immunosenescence and inflammaging.

Tissue Microenvironments

Different tissues comprise highly distinct milieus that impose context-dependent biochemical challenges on their resident cells, which further change when tissues age. Yet, it is not known how DCs and neutrophils survive in their different homing organs and maintain their functionality.

Hypothesis

I hypothesize that DCs and neutrophils have to adjust their metabolism to the distinct environments of their tissues of residence. This is important because metabolic changes upon stimulation have been shown to affect the functions of those cells in vitro.

Importance of Metabolic Adaptations

Given their power to orchestrate immune responses, it is now vital to reveal the precise metabolic adaptations of DCs and neutrophils to their distinct homing organs and to determine how that affects their activities. This pioneering knowledge will expose organ-dependent metabolic vulnerabilities of DCs and neutrophils to uphold their homeostatic and immune functions, which I envisage will cause their dysfunction in aging.

Research Approach

I will uncover the metabolic adaptations of DCs and neutrophils to over 10 healthy and aged tissues using independent innovative approaches and adapted cutting-edge techniques.

Objectives

1. Reveal the relevance of tissue-dependent metabolic adjustments for their presence and functions in organs.
2. Dissect the underlying molecular mechanisms.
3. Expose the tissue-specificity of DC and neutrophil dysfunction in aging and the role of their metabolism.

Impact on Translational Immunology

The discovery of tissue-dependent metabolic adaptations by DCs and neutrophils that impact their functions will transform translational immunology research to integrate the tissue context and reveal novel organ-specific therapeutic strategies to combat immune dysfunction in aging and beyond.