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VLA-1 Binding to Collagen IV Controls Effector T Cell Suppression by Myeloid-Derived Suppressor Cells in the Splenic Red Pulp
Please always quote using this URN: urn:nbn:de:bvb:20-opus-222671
- Myeloid-derived suppressor cells (MDSCs) represent a major population controlling T cell immune responses. However, little is known about their molecular requirements for homing and T cell interaction to mediate suppression. Here, we investigated the functional role of the homing and collagen IV receptor VLA-1 (α1β1-integrin) on in vitro GM-CSF generated murine MDSCs from wild-type (WT) and CD49a/α1-integrin (Itga1\(^{−/−}\)) gene-deficient mice. Here, we found that effector (Teff) but not naive (Tn) CD4\(^+\) T cells express VLA-1 andMyeloid-derived suppressor cells (MDSCs) represent a major population controlling T cell immune responses. However, little is known about their molecular requirements for homing and T cell interaction to mediate suppression. Here, we investigated the functional role of the homing and collagen IV receptor VLA-1 (α1β1-integrin) on in vitro GM-CSF generated murine MDSCs from wild-type (WT) and CD49a/α1-integrin (Itga1\(^{−/−}\)) gene-deficient mice. Here, we found that effector (Teff) but not naive (Tn) CD4\(^+\) T cells express VLA-1 and monocytes further up-regulated their expression after culture in GM-CSF when they differentiated into the monocytic subset of resting MDSCs (R-MDSCs). Subsequent activation of R-MDSCs by LPS+IFN-γ (A-MDSCs) showed increased in vitro suppressor potential, which was independent of VLA-1. Surprisingly, VLA-1 deficiency did not influence A-MDSC motility or migration on collagen IV in vitro. However, interaction times of Itga1\(^{−/−}\) A-MDSCs with Teff were shorter than with WT A-MDSCs on collagen IV but not on fibronectin substrate in vitro. After injection, A-MDSCs homed to the splenic red pulp where they co-localized with Teff and showed immediate suppression already after 6 h as shown by inhibition of T cell proliferation and induction of apoptosis. Injection of A-MDSCs from Itga1\(^{−/−}\) mice showed equivalent homing into the spleen but a reduced suppressive effect. Interaction studies of A-MDSCs with Teff in the subcapsular red pulp with intravital two-photon microscopy revealed also here that MDSC motility and migration parameters were not altered by VLA-1 deficiency, but the interaction times with Teff were reduced. Together, our data point to a new role of VLA-1 adhesion to collagen IV as a prerequisite for extended contact times with Teff required for suppression.…
Author: | Ina N. Eckert, Eliana Ribechini, Katja J. Jarick, Sandra Strozniak, Sarah J. Potter, Andreas Beilhack, Manfred B. Lutz |
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URN: | urn:nbn:de:bvb:20-opus-222671 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Virologie und Immunbiologie |
Medizinische Fakultät / Medizinische Klinik und Poliklinik II | |
Language: | English |
Parent Title (English): | Frontiers in Immunology |
ISSN: | 1664-3224 |
Year of Completion: | 2021 |
Volume: | 11 |
Article Number: | 616531 |
Source: | Frontiers in Immunology 2021, 11:616531. doi: 10.3389/fimmu.2020.616531 |
DOI: | https://doi.org/10.3389/fimmu.2020.616531 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | T cells; VLA-1; homing; myeloid-derived suppressor cells (MDSCs); spleen |
Release Date: | 2021/03/16 |
Date of first Publication: | 2021/01/18 |
Open-Access-Publikationsfonds / Förderzeitraum 2020 | |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |