Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives

Song, Xiayinan; Zhao, Shengxuan; Zhang, Weiheng; Wang, Yan; Zheng, Fengjie

doi:10.3390/biomedicines14092100

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Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives

by

Xiayinan Song

^1,†,

Shengxuan Zhao

^1,†,

Weiheng Zhang

¹,

Yan Wang

² and

Fengjie Zheng

^1,*

¹

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100105, China

²

Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150001, China

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Biomedicines 2026, 14(9), 2100; https://doi.org/10.3390/biomedicines14092100

Submission received: 29 July 2026 / Revised: 8 September 2026 / Accepted: 8 September 2026 / Published: 17 September 2026

(This article belongs to the Special Issue Immune Cell Reprogramming: Molecular Mechanisms and Therapeutic Approaches)

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Abstract

Despite advances in immunomodulatory therapies, dysregulated T-cell trafficking persists as a pathological cornerstone in chronic inflammation, autoimmunity, and cancer. This spatially precise navigation—orchestrated by receptor–ligand cascades—ensures immune surveillance but drives disease when impaired. Targeting individual receptors faces limitations due to functional redundancy. Emerging research establishes metabolic reprogramming as a critical regulator of trafficking efficiency, where glucose, amino acid, lipid, and mitochondrial metabolism dynamically control all stages: from chemotaxis, selectin-mediated rolling, and integrin-dependent adhesion to transendothelial migration and interstitial migration. Critically, these pathways integrate energy supply, metabolite signaling, and epigenetic modulation to influence T-cell trafficking fates. Here, we dissect how reprogramming core metabolic networks calibrates trafficking cascades and highlight therapeutic strategies targeting key nodes to correct pathological migration in autoimmunity, cancer, and transplantation.

Keywords: T cell; trafficking; metabolic reprogramming; immunotherapy

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MDPI and ACS Style

Song, X.; Zhao, S.; Zhang, W.; Wang, Y.; Zheng, F. Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives. Biomedicines 2026, 14, 2100. https://doi.org/10.3390/biomedicines14092100

AMA Style

Song X, Zhao S, Zhang W, Wang Y, Zheng F. Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives. Biomedicines. 2026; 14(9):2100. https://doi.org/10.3390/biomedicines14092100

Chicago/Turabian Style

Song, Xiayinan, Shengxuan Zhao, Weiheng Zhang, Yan Wang, and Fengjie Zheng. 2026. "Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives" Biomedicines 14, no. 9: 2100. https://doi.org/10.3390/biomedicines14092100

APA Style

Song, X., Zhao, S., Zhang, W., Wang, Y., & Zheng, F. (2026). Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives. Biomedicines, 14(9), 2100. https://doi.org/10.3390/biomedicines14092100

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives

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