VLA-1 Binding to Collagen IV Controls Effector T Cell Suppression by Myeloid-Derived Suppressor Cells in the Splenic Red Pulp

• Published in: Frontiers in immunology Vol. 11; p. 616531
• Main Authors: Eckert, Ina N, Ribechini, Eliana, Jarick, Katja J, Strozniak, Sandra, Potter, Sarah J, Beilhack, Andreas, Lutz, Manfred B
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 18.01.2021
• Subjects: homing; Immunology; myeloid-derived suppressor cells (MDSCs); spleen; T cells; VLA-1; VLA-1; myeloid-derived suppressor cells (MDSCs); homing; T cells; spleen
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.616531

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 GM-CSF generated murine MDSCs from wild-type (WT) and CD49a/α1-integrin ( ) 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 suppressor potential, which was independent of VLA-1. Surprisingly, VLA-1 deficiency did not influence A-MDSC motility or migration on collagen IV . However, interaction times of A-MDSCs with Teff were shorter than with WT A-MDSCs on collagen IV but not on fibronectin substrate . 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 1 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.