Crawling of effector T cells on extracellular matrix: role of integrins in interstitial migration in inflamed tissues

Kim, Chang H.

doi:10.1038/cmi.2013.47

Cited by 10 publications

(5 citation statements)

References 14 publications

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“…In contrast to findings of a previous study in human tissue [21], the present data show that GLT25D2 is broadly expressed in the spleen, thymus, and other tissues of mice. This expression difference may be due to species differences.…”

Section: Cd69contrasting

confidence: 99%

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Glt25d2 Knockout Directly Increases CD25+CD69– but Decreases CD25–CD69+ Subset Proliferation and is Involved in Concanavalin-Induced Hepatitis

Hao

Liu

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The elaborate structure of the extracellular matrix (ECM) and the appropriate surface glycoforms upon it are indispensable to CD4⁺ T cell regulation. Methods: To explore the effects of Glcα1,2Galβ1 glycosylation mediated by GLT25D2 (Colgalt2) for CD4⁺ T cell regulation, we prepared C57BL/6J Glt25d2^-/- mice. In the induction of hepatitis, after concanavalin A (Con A) challenge for 6, 12, and 24 h, more extensive parenchymal injury was noted in Glt25d2^-/- mice than in wild-type (WT) mice at 12 h. Immunohistochemistry and laser scanning confocal microscopy were used to detect GLT25D2 expression, and subsets of CD4⁺T cells was analyzed by flow cytometry. A total of 26 cytokines in serum samples were determined using Luminex technology. Results: The trend in liver injury score variation was consistent with serum alanine aminotransferase and aspartate aminotransferase levels. The levels of interleukin 4 (IL-4), IL-1β, IL-9, and several chemokines such as macrophage inflammatory protein-2, eotaxin, and growth-related oncogene α were significantly increased in Glt25d2^-/- mice compared with WT mice after Con A challenge. A further phenotype analysis of primary Glt25d2^-/- CD4⁺ T cells showed that Glt25d2 knockout increased the frequency of the CD25⁺CD69^- subset but decreased the frequency of the CD25^-CD69⁺ subset after Con A challenge for 6, 12, and 24 h compared with those of WT CD4⁺ T cells. Activation-induced apoptosis was also significantly increased in Glt25d2^-/- CD4⁺ T cells after Con A challenge compared with WT CD4⁺ T cells. Lectin microarray hybridization showed that Glt25d2 knockout increased the binding activity of Narcissus pseudonarcissus lectin to CD4⁺ T cells but Amaranthus caudatus lectin–binding activity was lost during Con A challenge. Conclusion: The present results suggest that collagen glycosylation mediated by GLT25D2 may regulate a subset of CD4⁺ T cells and be involved in the pathogenesis of Con A–induced hepatitis.

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Section: Cd69contrasting

confidence: 99%

“…Many components of the ECM are correlated with CD4 + T lymphocyte regulation, such as laminins [19], proteoglycan aggrecans [20], and integrin [21,22]. The co-culturing of CD4 + T cells with fibroblasts significantly increased the secretion of IL-17 and other cytokines [23].…”

Section: Introductionmentioning

confidence: 99%

Glt25d2 Knockout Directly Increases CD25+CD69– but Decreases CD25–CD69+ Subset Proliferation and is Involved in Concanavalin-Induced Hepatitis

Hao

Liu

Zhang

et al. 2018

Cell Physiol Biochem

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“…This behavior contrasts with the increased mesenchymal stem cell spreading on increased RGD-functionalized PLLA surfaces. At the same time, it is in line with the utilization of integrins during their trans-endothelial and interstitial migration [86]. It is also in line with the ability of T-cells in vivo to squeeze through diameters smaller than those of average T-cells based on physiological conditions when responding to immune signals [87], providing an explanation for our observations at high RGD surface densities.…”

Section: Discussionsupporting

confidence: 83%

Investigating Cancerous Exosomes’ Effects on CD8+ T-Cell IL-2 Production in a 3D Unidirectional Flow Bioreactor Using 3D Printed, RGD-Functionalized PLLA Scaffolds

Karami

Srivastava

Ramesh

et al. 2022

JFB

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Exosomes from cancer cells are implicated in cancer progression and metastasis, carrying immunosuppressive factors that limit the antitumor abilities of immune cells. The development of a real-time, 3D cell/scaffold construct flow perfusion system has been explored as a novel tool in the study of T-cells and exosomes from cancer cells. Exosomes from human lung cancer (H1299 and A549) cells were co-cultured in a unidirectional flow bioreactor with CD8+ T-cells immobilized onto 3D-printed RGD-functionalized poly(L-lactic) acid (PLLA) scaffolds and assessed for IL-2 production. The IL-2 production was investigated for a wide range of T-cell to exosome ratios. With the successful incorporation of the RGD binding motif onto the PLLA surface at controllable densities, CD8+ T-cells were successfully attached onto 2D disks and 3D printed porous PLLA scaffolds. T-cell attachment increased with increasing RGD surface density. The diameter of the attached T-cells was 7.2 ± 0.2 µm for RGD densities below 0.5 nmoles/mm2 but dropped to 5.1 ± 0.3 µm when the RGD density was 2 nmoles/mm2 due to overcrowding. The higher the number of cancer exosomes, the less the IL-2 production by the surface-attached T-cells. In 2D disks, the IL-2 production was silenced for T-cell to exosome ratios higher than 1:10 in static conditions. IL-2 production silencing in static 3D porous scaffolds required ratios higher than 1:20. The incorporation of flow resulted in moderate to significant T-cell detachment. The portions of T-cells retained on the 3D scaffolds after exposure for 4 h to 0.15 or 1.5 mL/min of perfusion flow were 89 ± 11% and 30 ± 8%, respectively. On 3D scaffolds and in the presence of flow at 0.15 ml/min, both H1299 and A549 cancerous exosomes significantly suppressed IL-2 production for T-cell to exosome ratios of 1:1000. The much higher level of exosomes needed to silence the IL-2 production from T-cells cultured under unidirectional flow, compared to static conditions, denotes the importance of the culturing conditions and the hydrodynamic environment, on the interactions between CD8+ T-cells and cancer exosomes.

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“…The CTLs proximal to tumor cells exhibited downregulation of LAMA1/4, TNC, and ITGA6 compared to those distal from tumor cells, suggesting enhanced T cell mobility and improved penetration into the tumor parenchyma 35,36 ( Figure S2E ). Plasma cells located distant from vessels and closer to the tumor upregulated the stress responses, interleukin-3/5, and GM-CSF, along with increased chemotaxis response.…”

Section: Resultsmentioning

confidence: 99%

Deciphering functional tumor-immune crosstalk through highly multiplexed imaging and deep visual proteomics

Zheng,

Mund,

Mann

2024

Preprint

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Deciphering the intricate tumor–immune interactions within the microenvironment is crucial for advancing cancer immunotherapy. Here, we developed a novel approach integrating highly multiplexed imaging, laser microdissection, and deep visual proteomics (DVP) to spatially profile the proteomes of 21 distinct cell populations in human colorectal and tonsil cancers with high sensitivity. We selected colorectal tumor as an example of a cold tumor, uncovering an immunosuppressive macrophage barrier impeding T cell infiltration and regionally altering lymphocyte proteomes. Spatial proteomic analysis revealed distinct functional states of T cells in different tumor compartments. In tonsil cancer – a hot tumor, we identified significant heterogeneity of cell proteomes influenced by proximity to cytotoxic T cell subtypes. Tumor–infiltrating T cells exhibited metabolic adaptations and enhanced stress resilience, enabling migration into hypoxic regions. Our spatially–resolved, highly multiplexed strategy deciphers the complex cellular interplay within the tumor microenvironment, with implications for identifying new immunotherapy targets and signatures.

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Crawling of effector T cells on extracellular matrix: role of integrins in interstitial migration in inflamed tissues

Cited by 10 publications

References 14 publications

Glt25d2 Knockout Directly Increases CD25+CD69– but Decreases CD25–CD69+ Subset Proliferation and is Involved in Concanavalin-Induced Hepatitis

Glt25d2 Knockout Directly Increases CD25+CD69– but Decreases CD25–CD69+ Subset Proliferation and is Involved in Concanavalin-Induced Hepatitis

Investigating Cancerous Exosomes’ Effects on CD8+ T-Cell IL-2 Production in a 3D Unidirectional Flow Bioreactor Using 3D Printed, RGD-Functionalized PLLA Scaffolds

Deciphering functional tumor-immune crosstalk through highly multiplexed imaging and deep visual proteomics

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