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Migration arrest and transendothelial trafficking of human pathogenic-like Th17 cells are mediated by differentially positioned chemokines

Author

Listed:
  • Farhat Parween

    (National Institutes of Health)

  • Satya P. Singh

    (National Institutes of Health)

  • Nausheen Kathuria

    (National Institutes of Health)

  • Hongwei H. Zhang

    (National Institutes of Health)

  • Shinji Ashida

    (National Institutes of Health)

  • Francisco A. Otaizo-Carrasquero

    (National Institutes of Health)

  • Amirhossein Shamsaddini

    (National Institutes of Health)

  • Paul J. Gardina

    (National Institutes of Health)

  • Sundar Ganesan

    (National Institutes of Health)

  • Juraj Kabat

    (National Institutes of Health)

  • Hernan A. Lorenzi

    (National Institutes of Health)

  • Deanna J. Riley

    (National Institutes of Health)

  • Timothy G. Myers

    (National Institutes of Health)

  • Stefania Pittaluga

    (National Institutes of Health)

  • Bibiana Bielekova

    (National Institutes of Health)

  • Joshua M. Farber

    (National Institutes of Health)

Abstract

Human Th17/type 17 cells express the chemokine receptor CCR6, but the functions of CCR6 and other chemokine receptors in human type 17 Th cell extravasation have not been fully delineated. Here we show that human peripheral blood CD4+CCR6+ T cells co-expressing CCR2 have a pathogenic Th17 signature, can produce inflammatory cytokines without T cell receptor activation, and show enhanced expression of pathogenicity-associated and activation-associated genes in the cerebrospinal fluid of patients with multiple sclerosis as compared to controls. In flow chambers with activated endothelial cell (EC) monolayers, CD4+CCR6+CCR2+ T cells are efficient at transendothelial migration (TEM). Ligands for CCR5, CCR6 and CXCR3 localize to EC surfaces and mediate only arrest, whereas CCR2 ligands fail to bind well to ECs and mediate only TEM. Conversely, expressing a chimeric CCR2 ligand engineered to bind glycosaminoglycans on ECs results in CCR2-mediated arrest but blocks TEM induction. Our results from human pathogenic-like type 17 cells thus suggest that T cell migration arrest requires chemokine bound to EC surfaces, whereas TEM requires a transendothelial chemokine gradient.

Suggested Citation

  • Farhat Parween & Satya P. Singh & Nausheen Kathuria & Hongwei H. Zhang & Shinji Ashida & Francisco A. Otaizo-Carrasquero & Amirhossein Shamsaddini & Paul J. Gardina & Sundar Ganesan & Juraj Kabat & He, 2025. "Migration arrest and transendothelial trafficking of human pathogenic-like Th17 cells are mediated by differentially positioned chemokines," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57002-6
    DOI: 10.1038/s41467-025-57002-6
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    References listed on IDEAS

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    1. Hong-Gyun Lee & Jae-Ung Lee & Do-Hyun Kim & Sangho Lim & Insoo Kang & Je-Min Choi, 2019. "Pathogenic function of bystander-activated memory-like CD4+ T cells in autoimmune encephalomyelitis," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
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