DC 13 -The role of tissue microenvironment on cardiolipin deficiency-mediated inflammation.

• Objectives:

Aim of the project: To uncover how tissue microenvironments and cardiolipin metabolism dysfunctions reciprocally shape each other, driving tissue-specific immune imbalance and inflammation.

1. analyse the multi-organ inflammatory profile driven by cardiolipin deficiency;
2. explore how the tissue microenvironment affects immune cell function in cardiolipin deficiency;
3. define the local metabolic and lipidomic environment in cardiolipin-deficient models;
4. explore therapeutic modulation of cardiolipin metabolism to restore immune homeostasis and limit inflammation.

• Brief project description:

T cells rely on tightly regulated mitochondrial lipid metabolism, including cardiolipin synthesis, to support activation, differentiation, and immune function. When mitochondrial function is compromised—such as through defects in cardiolipin synthesis—T cells undergo metabolic rewiring, lose functional capacity, and can no longer maintain the balance between pro- and anti-inflammatory signals required for tissue homeostasis.

Across the body, tissues exhibit strikingly different levels of sensitivity to these T-cell metabolic defects, suggesting that microenvironmental cues dictate whether dysfunctional T cells trigger local inflammation or remain controlled. This implies a reciprocal relationship: mitochondrial deficiencies alter how T cells respond to their environment, while tissue-specific metabolic and lipidomic landscapes may shape how T cells adapt—or fail to adapt—to mitochondrial stress.

• Planned secondments:

Rafael Argüello lab (Centre d’Immunologie de Marseille-Luminy, France)
• Learn Spatial-SCENITH to map immune cell metabolism in vivo.

Zezina lab (Sanofi, Germany)
• Training on spatial metabolomics and lipidomics techniques to map metabolic landscapes across organs.