WKYMVm Works by Targeting Immune Cells

Abstract

WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met) is a synthetic hexapeptide identified as a potent agonist of FPRs. FPRs are widely expressed on the cell membrane of immune cells. Therefore, WKYMVm participates in the regulation of immune cells by activating FPRs, and plays a therapeutic role in infections, tumors, autoimmune diseases and so on. WKYMVm can promote the chemotactic migration, increase the bactericidal activity of neutrophils and monocytes. WKYMVm also regulates the number and polarization of macrophages, affects the maturation of DCs and the differentiation of T cells, and promotes the activation and chemotaxis of NK cells. These functions make WKYMVm a candidate drug for immunotherapy. In this paper, we summarize the regulatory effects and underlying mechanisms of WKYMVm on six immune cells (neutrophils, monocytes, macrophages, DCs, T cells and NK cells) to increase comprehensive understanding and promote further research on WKYMVm.

Keywords:

• WKYMVm
• FPRs
• immune cells
• chemotaxis
• polarization

Abbreviations

WKYMVm, Trp-Lys-Tyr-Met-Val-D-Met; FPRs, formyl peptide receptors; DCs, dendritic cells; NK, natural killer; pM, picomolar; nM, nanomolar; IL-6, interleukin-6; STAT3, signal transducer and activator of transcription 3; ERK, extracellular-signal-regulated kinase; NF-κB, nuclear factor κB; PLC, phospholipase C; PI3Kγ, phosphatidylinositol 3-kinase γ; PIP2, phosphoinositol-4,5-bisphosphate; DAG, diacylglycerol; IP3, inositol 1,4,5-trisphosphate; AKT, protein kinase B; PKC, protein kinase C; MAPK, mitogen-activated protein kinase; ROS, reactive oxygen species; NETs, neutrophil extracellular traps; MPO, myeloperoxidase; SOD, superoxide dismutase; LTB4, leukotriene B4; cPLA₂, cytosolic phospholipase A₂; AA, arachidonic acid; 5-LO, 5-lipoxygenase; p125FAK, focal adhesion kinase; Pyk2, proline-rich tyrosine kinase 2; PLD₁, phospholipase D₁; TNF-α, tumor necrosis factor α; IL-1β, interleukin-1β; IL-10, interleukin-10; TGF-β, transforming growth factor β; IL-1α, interleukin-1α; JAK1, Janus kinase 1; PPARγ, peroxisome proliferator-activated receptor γ; ISG15, interferon-stimulating gene 15; TFEB, transcription factor EB; mBMSCs, mouse bone marrow-derived mesenchymal stem cells; PDGF-BB, platelet-derived growth factor-BB; CTLs, cytotoxic T lymphocytes; BMDCs, bone marrow-derived dendritic cells; IFN-γ, interferon-γ; 5-FU, 5-fluorouracil; mDCs, mature dendritic cells; IL-12, interleukin-12; Th1, helper T cell 1; Th17, helper T cell 17; MODCs, monocyte-derived dendritic cells; LPS, lipopolysaccharide; HLA-DR, human leukocyte antigen DR; IL-2, interleukin-2; JNK, c-Jun N-terminal kinase.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by the Medical Science Research Project of Dalian (No. 2112015), the National Natural Science Foundation of China (No. 82100620) and the Doctoral Startup Research Fund of Liaoning Province (2021-BS-218).