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

Ujagar, N. S.; Poudel, S.; Saraswat, S.; Sureshchandra, S.; Kim, J.; Le, U.-V.; Jones, A. R.; Hopkins, N.; Sriram, T.; Matson, M.; Pilier, E. H.; Mejia, M.; Bailin, S. S.; Wanjalla, C. N.; Sy, M. Y.; Newcomb, D. C.; Walsh, C.; Wagar, L. E.; Nikolajczyk, B. S.; Zhang, X. D.; Green, D. R.; Nicholas, D. A.

doi:10.64898/2026.09.01.748572

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bioRxiv · 10.64898/2026.09.01.748572

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

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Abstract

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.

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Ujagar, N. S., Poudel, S., Saraswat, S., Sureshchandra, S., Kim, J., Le, U.-V., Jones, A. R., Hopkins, N., Sriram, T., Matson, M., Pilier, E. H., Mejia, M., Bailin, S. S., Wanjalla, C. N., Sy, M. Y., Newcomb, D. C., Walsh, C., Wagar, L. E., Nikolajczyk, B. S., Zhang, X. D., Green, D. R., Nicholas, D. A.. 2026-09-06. A Single-Cell Framework for Classifying Human Th17 Pathogenicity Links Acylcarnitine Metabolism to Non-Pathogenic Inflammation in Type 2 Diabetes. https://doi.org/10.64898/2026.09.01.748572

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