Galectin-9 supports primary T cell transendothelial migration in a glycan and integrin dependent manner

Adel Abo Mansour, Federica Raucci, Mustafa Sevim, Anella Saviano, Jenefa Begum, Zhaogong Zhi, Laleh Pezhman, Samantha Tull, Francesco Maione, Asif Jilani Iqbal

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Abstract

Adaptive immunity relies on the efficient recruitment of T cells from the blood into peripheral tissues. However, the current understanding of factor(s) coordinating these events is incomplete. Previous studies on galectin-9 (Gal-9), have proposed a functionally significant role for this lectin in mediating leukocyte adhesion and transmigration. However, very little is known about its function in T cell migration. Here, we have investigated the role of the Gal-9 on the migration behaviour of both human primary CD4 + and CD8 + T cells. Our data indicate that Gal-9 supports both CD4 + and CD8 + T cell adhesion and transmigration in a glycan dependent manner, inducing L-selectin shedding and upregulation of LFA-1 and CXCR4 expression. Additionally, when immobilized, Gal-9 promoted capture and firm adhesion of T cells under flow, in a glycan and integrin-dependent manner. Using an in vivo model, dorsal air pouch, we found that Gal-9 deficient mice display impaired leukocyte trafficking, with a reduction in pro-inflammatory cytokines/chemokines generated locally. Furthermore, we also demonstrate that Gal-9 inhibits the chemotactic function of CXCL12 through direct binding. In conclusion, our study characterises, for the first time, the capture, adhesion, and migration behaviour of CD4 + and CD8 + T cells to immobilised /endothelial presented Gal-9, under static and physiological flow conditions. We also demonstrate the differential binding characteristics of Gal-9 to T cell subtypes, which could be of potential therapeutic significance, particularly in the treatment of inflammatory-based diseases, given Gal-9 ability to promote apoptosis in pathogenic T cell subsets.

Original languageEnglish
Article number113171
Number of pages13
JournalBiomedicine and Pharmacotherapy
Volume151
Early online date25 May 2022
DOIs
Publication statusPublished - Jul 2022

Bibliographical note

Funding Information:
AAM is supported by a King Khalid University funded scholarship ( 57875 ). FR is supported by a University of Naples Federico II PhD scholarship in Pharmaceutical Sciences. AS is supported by a Dompé Farmaceutici S.p.A fellowship for PhD programme in “Nutraceuticals, functional foods and human health” (University of Naples Federico II). AJI is supported by a Birmingham Fellowship.

Publisher Copyright:
© 2022 The Authors

Keywords

  • Animals
  • CD8-Positive T-Lymphocytes
  • Galectins
  • Integrins
  • Mice
  • Polysaccharides
  • Transendothelial and Transepithelial Migration

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