Nikolajczyk, B. S. | bioRxiv Science

bioRxiv2026

A Single-Cell Framework for Classifying Human Th17 Pathogenicity Links Acylcarnitine Metabolism to Non-Pathogenic Inflammation in Type 2 Diabetes

Based on in vitro and animal studies, Th17 cells are classified as pathogenic (pTh17) or non-pathogenic (nTh17), but the inability to identify these subsets in primary human samples limits translation. We developed a single-cell ELISA to enrich human Th17s, enabling transcriptomic and flow-cytometric classification. nTh17 cells predominated in Type 2 diabetes and exhibited signatures of acylcarnitine synthesis, while knockdown of CPT1A demonstrated that acylcarnitine metabolism regulates Th17 pathogenicity.

immunology↗

bioRxiv2024

Mitochondria-Associated Membranes Are Not Altered In Immune Cells In T2D

Metabolism research is increasingly recognizing the contributions of organelle crosstalk to metabolic regulation. Mitochondria-associated membranes (MAMs), which are structures connecting the mitochondria and endoplasmic reticulum (ER), are critical in a myriad of cellular functions linked to cellular metabolism. MAMs control calcium signaling, mitochondrial transport, redox balance, protein folding/degradation, and in some studies, metabolic health. The possibility that MAMs drive changes in cellular function in individuals with Type 2 Diabetes (T2D) is controversial. Although disruptions in MAMs that change the distance between the mitochondria and ER, MAM protein composition, or disrupt downstream signaling, can perpetuate inflammation, one key trait of T2D. However, the full scope of this structures role in immune cell health and thus T2D-associated inflammation remains unknown. We show that human immune cell MAM proteins and their associated functions are not altered by T2D and thus unlikely to contribute to metaflammation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/586170v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1a281f1org.highwire.dtl.DTLVardef@1025corg.highwire.dtl.DTLVardef@42259eorg.highwire.dtl.DTLVardef@b3bbb1_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗