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

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, Hernan A. Lorenzi, Deanna J. Riley, Timothy G. Myers, Stefania Pittaluga, Bibiana Bielekova and Joshua M. Farber ()
Additional contact information
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

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57002-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57002-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57002-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().