Fractalkine produced by Shiga toxin type 2-stimulated human glomerular endothelial cells modulates γδ T lymphocyte migration
5 affiliations
- 1Instituto de Medicina Experimental – CONICET – Academia Nacional de Medicina
- 2Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires
- 3Laboratorio de Fisiopatogenia, Departamento de Ciencias Fisiológicas, Facultad de Ciencias Médicas, Universidad de Buenos Aires
- 4Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay), CONICET – Universidad de Buenos Aires
- 5Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires
Abstract
Introduction: γδ T cells play a critical role in tissue immunosurveillance through their capacity to sense cellular stress. However, their recruitment dynamics to peripheral organs such as kidney during Shiga toxin (Stx)–induced renal damage, remain undefined. Since the CX ₃ CL1/CX ₃ CR1 axis is vital for leukocyte homing into inflamed organs, we investigated its participation in mediating γδ T cell trafficking to the Stx–damaged kidney.
Material: We integrated in vitro functional assays using Stx2a-stimulated human glomerular endothelial cells (HGEC) with in silico single-cell RNA sequencing (scRNA–seq) analysis of public human kidney injury datasets. CX ₃ CL1/CX ₃ CR1 expression was evaluated via qPCR, ELISA, and flow cytometry, while the functional recruitment γδ T cells recruitment was quantified using transwell migration assays.
Results: In vitro , Stx2a significantly upregulates CX3CL1 mRNA and protein secretion in HGEC. In silico profiling of acute kidney injury (AKI) tissues confirmed widespread CX3CL1 upregulation in the damaged parenchyma and identified a distinct TRGV9 + cell cluster expressing CX3CR1 transcripts. Contingency analysis showed that TRGV9 + cells were substantially more likely to express CX3CR1 than other T/NKT cells. Importantly, flow cytometry analysis confirmed that γδ T cells express high levels of CX ₃ CR1 protein. Finally, transwell assays demonstrated that both Stx2a-conditioned HGEC media and recombinant CX ₃ CL1 potently induce γδ T cell migration, an effect that was completely abrogated upon disruption of the chemokine gradient.
Discussion: Together, these findings suggest that CX ₃ CL1 release by Stx2a-stimulated endothelial cells contributes to a chemotactic gradient that may mediate the targeted recruitment of circulating CX3CR1 + TRGV9/TRDV2 cells to the injured kidney.
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BibTeX
@article{rosso2026fractalkine,
title = {{Fractalkine produced by Shiga toxin type 2-stimulated human glomerular endothelial cells modulates γδ T lymphocyte migration}},
author = {David Antonio Rosso and Micaela Rosato and Martín Ledesma and Fernando Daniel Gómez and Irene Angélica Keitelman and Florencia Sabbione and Analía Silvina Trevani and María Marta Amaral and Carolina Cristina Jancic},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1925614},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1925614/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Fractalkine produced by Shiga toxin type 2-stimulated human glomerular endothelial cells modulates γδ T lymphocyte migration
AU - David Antonio Rosso
AU - Micaela Rosato
AU - Martín Ledesma
AU - Fernando Daniel Gómez
AU - Irene Angélica Keitelman
AU - Florencia Sabbione
AU - Analía Silvina Trevani
AU - María Marta Amaral
AU - Carolina Cristina Jancic
PY - 2026
DA - 2026/10/27
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1925614
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1925614/full
AB - Introduction: γδ T cells play a critical role in tissue immunosurveillance through their capacity to sense cellular stress. However, their recruitment dynamics to peripheral organs such as kidney during Shiga toxin (Stx)–induced renal damage, remain undefined. Since the CX ₃ CL1/CX ₃ CR1 axis is vital for leukocyte homing into inflamed organs, we investigated its participation in mediating γδ T cell trafficking to the Stx–damaged kidney. Material: We integrated in vitro functional assays using Stx2a-stimulated human glomerular endothelial cells (HGEC) with in silico single-cell RNA sequencing (scRNA–seq) analysis of public human kidney injury datasets. CX ₃ CL1/CX ₃ CR1 expression was evaluated via qPCR, ELISA, and flow cytometry, while the functional recruitment γδ T cells recruitment was quantified using transwell migration assays. Results: In vitro , Stx2a significantly upregulates CX3CL1 mRNA and protein secretion in HGEC. In silico profiling of acute kidney injury (AKI) tissues confirmed widespread CX3CL1 upregulation in the damaged parenchyma and identified a distinct TRGV9 + cell cluster expressing CX3CR1 transcripts. Contingency analysis showed that TRGV9 + cells were substantially more likely to express CX3CR1 than other T/NKT cells. Importantly, flow cytometry analysis confirmed that γδ T cells express high levels of CX ₃ CR1 protein. Finally, transwell assays demonstrated that both Stx2a-conditioned HGEC media and recombinant CX ₃ CL1 potently induce γδ T cell migration, an effect that was completely abrogated upon disruption of the chemokine gradient. Discussion: Together, these findings suggest that CX ₃ CL1 release by Stx2a-stimulated endothelial cells contributes to a chemotactic gradient that may mediate the targeted recruitment of circulating CX3CR1 + TRGV9/TRDV2 cells to the injured kidney.
SN - 1664-3224
ER -