دورية أكاديمية
VLA-1 Binding to Collagen IV Controls Effector T Cell Suppression by Myeloid-Derived Suppressor Cells in the Splenic Red Pulp
| العنوان: | VLA-1 Binding to Collagen IV Controls Effector T Cell Suppression by Myeloid-Derived Suppressor Cells in the Splenic Red Pulp |
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| المؤلفون: | Eckert, Ina N., Ribechini, Eliana, Jarick, Katja J., Strozniak, Sandra, Potter, Sarah J., Beilhack, Andreas, Lutz, Manfred B. |
| سنة النشر: | 2021 |
| المجموعة: | Würzburg University: Online Publication Service |
| مصطلحات موضوعية: | ddc:610 |
| الوصف: | 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 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/22267Test; urn:nbn:de:bvb:20-opus-222671; https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-222671Test; https://doi.org/10.3389/fimmu.2020.616531Test; https://opus.bibliothek.uni-wuerzburg.de/files/22267/fimmu-11-616531.pdfTest |
| DOI: | 10.3389/fimmu.2020.616531 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2020.616531Test https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/22267Test https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-222671Test https://opus.bibliothek.uni-wuerzburg.de/files/22267/fimmu-11-616531.pdfTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0/deed.deTest ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.28AE9C60 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2020.616531 |
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