Mitochondrial DNA Programs Lactylation of cGAS to Induce IFN Responses in Patients with Systemic Lupus Erythematosus.

Mitochondrial DNA (mtDNA) is frequently released from mitochondria, activating cGAS-STING signaling and inducing type I IFNs (IFN-Is) in systemic lupus erythematosus (SLE). Meanwhile, whether and how the glycolytic pathway was involved in such IFN-I responses in human SLE remain unclear. In this study, we found that monocytes from SLE patients exerted robust IFN-I generation and elevated level of cytosolic mtDNA.

Mitochondrial Control of Proteasomal Psmb5 Drives the Differentiation of Tissue-Resident Memory T Cells in Patients with Rheumatoid Arthritis.

Objective: To explore T cell-intrinsic mechanisms underpinning the mal-differentiation of tissue-resident memory T (Trm) cells in patients with rheumatoid arthritis (RA).

Methods: Circulating T cells from patient with RA and healthy individuals were used for Trm cell differentiation. The role of Hobit in Trm differentiation was investigated through targeted silencing experiments.

Cancer CD39 drives metabolic adaption and mal-differentiation of CD4 T cells in patients with non-small-cell lung cancer.

While ectonucleotidase CD39 is a cancer therapeutic target in clinical trials, its direct effect on T-cell differentiation in human non-small-cell lung cancer (NSCLC) remains unclear. Herein, we demonstrate that human NSCLC cells, including tumor cell lines and primary tumor cells from clinical patients, efficiently drive the metabolic adaption of human CD4 T cells, instructing differentiation of regulatory T cells while inhibiting effector T cells. Of importance, NSCLC-induced T-cell mal-differentiation primarily depends on cancer CD39, as this can be fundamentally blocked by genetic depletion of CD39 in NSCLC.

Mitochondrial Control for Healthy and Autoimmune T Cells.

T cells are critical players in adaptive immunity, driving the tissue injury and organ damage of patients with autoimmune diseases. Consequently, investigations on T cell activation, differentiation, and function are valuable in uncovering the disease pathogenesis, thus exploring promising therapeutics for autoimmune diseases. In recent decades, accumulating studies have pinpointed immunometabolism as the fundamental determinant in controlling T cell fate.