Ly6C⁺Ly6G⁻ Myeloid‐derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury

Abstract

Acute inflammation is a prominent feature of central nervous system (CNS) insult and is detrimental to the CNS tissue. Although this reaction spontaneously diminishes within a short period of time, the mechanism underlying this inflammatory resolution remains largely unknown. In this study, we demonstrated that an initial infiltration of Ly6C + Ly6G À immature monocyte fraction exhibited the same characteristics as myeloid-derived suppressor cells (MDSCs), and played a critical role in the resolution of acute inflammation and in the subsequent tissue repair by using mice spinal cord injury (SCI) model. Complete depletion of Ly6C + Ly6G À fraction prior to injury by anti-Gr-1 antibody (clone: RB6-8C5) treatment significantly exacerbated tissue edema, vessel permeability, and hemorrhage, causing impaired neurological outcomes.Functional recovery was barely impaired when infiltration was allowed for the initial 24 h after injury, suggesting that MDSC infiltration at an early phase is critical to improve the neurological outcome. Moreover, intraspinal transplantation of ex vivo-generated MDSCs at sites of SCI significantly reduced inflammation and promoted tissue regeneration, resulting in better functional recovery. Our findings reveal the crucial role of an Ly6C + Ly6G À fraction as MDSCs in regulating inflammation and tissue repair after SCI, and also suggests an MDSC-based strategy that can be applied to acute inflammatory diseases.

Innate Immune Pathways Associated with Lung Radioprotection by Soy Isoflavones

“…Our findings are in agreement with other studies reporting that Arg-1 could attenuate the function of iNOS, inhibit NF-κB activation and inflammatory cytokines in vitro , and decrease macrophage infiltration and inflammation in vivo in a rabbit model of atherosclerosis (22). MDSCs played a critical role in the resolution of acute inflammation and tissue repair caused by spinal cord injury (30) and were found to modulate macrophage activation toward an immunosuppressive phenotype through Arg-1 (31). Whether early protection of Arg-1 + MDSC by soy isoflavones plays a role in altering molecular pathways involved in radiation-induced inflammation such as NF-κB activation and pro-inflammatory cytokine production remains to be established.…”

Reprogramming the lung microenvironment by inhaled immunotherapy fosters immune destruction of tumor

“…[11][12][13] Studies have demonstrated a suppressive effect of MDSC on NK cells through cell contact-dependent mechanisms [2][3][4][5] ; moreover, MDSC might play an immunosuppressive role in NK cell activation, exacerbating macrophage polarization toward an M2 phenotype. 6 To generate a more permissive microenvironment for NK cell activation by aerosolized TLR agonists, we tested the possibility that delivery of nebulized RB6-8C5 antibody, reported to reduce both monocytic and granulocytic subsets from circulating blood, 14 locally depletes MDSC. Indeed, flow cytometry analysis of enzymatically digested lungs of C57BL/6 mice injected i.v.…”

“…14 Airway-delivered RB6-8C5 antibody, directed to both Ly6G and Ly6C, at 72-96 h interval effectively depleted MDSC recruited in the lung tumor microenvironment at a dose 4-to 8-fold lower than that used in systemic administration, 14,19 improving antitumor effects of aerosolized TLR agonists. Although RB6-8C5 antibody is not only MSDCs specific, but can also target other Ly6G-or Ly6C-expressing cells, at a late time point of the experiment no differences in the percentage of macrophages, DCs , monocytes and CD8 C T cells were observed in the lungs.…”

Mesenchymal Stem/Stromal Cells Protect against Autoimmunity via CCL2-Dependent Recruitment of Myeloid-Derived Suppressor Cells

“…injected to mice three times at days 21 (24 h prior to immunization), 0 (the day of immunization), and 1 (the day after immunization) (26)(27)(28)(29)(30).…”