Katsouda et al. describe the impact of the sulfide species–generating enzyme MPST in energy homeostasis and metabolic health. Mpst^−/− mice placed on high-fat diet exhibit attenuated mitochondrial protein import, mitochondrial dysfunction, enhanced lipid accumulation, adipocyte enlargement, and excessive weight gain. Therapeutic sulfide administration ameliorates obesity-related molecular and phenotypic changes.

This study shows that Crohn’s disease–associated microbiota generate lysophosphatidylserines that promote Th1 responses by fueling glycolysis. Lysophosphatidylserine-induced aggravation of colitis is prevented by P2y10 deficiency in CD4⁺ T cells, demonstrating that dysbiotic microbiota-derived LysoPS exacerbates colitis by modulating Th1 cell metabolism.

Antigen stimulation induces a subset of CD4⁺ and CD8⁺ T cells to differentiate into CD4⁺CD8⁺ T cell subsets gaining in polyfunctional characteristics within the tumor. Monitoring CD4⁺CD8⁺ T cells may thus favor the identification and selection of antigen-reactive T cells to drive clinical benefit.

Kanbar et al. show that the long noncoding RNA Malat1 impacts the differentiation of effector and memory CD8⁺ T cell subsets by virtue of preferential epigenetic repression of memory-associated genes in terminal effector cells through an interaction with Ezh2.

Neuroimmune interaction influences essential CNS processes. Hanuscheck et al. report on the expression of interleukin-4 receptor alpha at presynaptic terminals in mouse and the human brain. The modulation of neuronal IL-4R signaling alters the neuronal transcriptome, impacts synaptic transmission, and causes anxiety-related behavior.

Local inflammation spreads to remote positions via sensory neuron–interneuron crosstalk using ATP. This neural pathway, or remote inflammation gateway reflex, may be a therapeutic target for inflammatory diseases with remote inflammation, such as rheumatoid arthritis.

Yao et al. describe GIMAP6 deficiency in humans and mice showing immune dysfunction and susceptibility to bacterial infections. They find impaired autophagy in GIMAP6-deficient immune cells and define a functional complex composed of GIMAP6, GIMAP7, and GABARAPL2.