More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis

Abstract

Monocyte chemoattractant protein-1 (MCP-1/CCL2) is renowned for its ability to drive the chemotaxis of myeloid and lymphoid cells. It orchestrates the migration of these cell types both during physiological immune defense and in pathological circumstances, such as autoimmune diseases including rheumatoid arthritis and multiple sclerosis, inflammatory diseases including atherosclerosis, as well as infectious diseases, obesity, diabetes, and various types of cancer. However, new data suggest that the scope of CCL2's functions may extend beyond its original characterization as a chemoattractant. Emerging evidence shows that it can impact leukocyte behavior, influencing adhesion, polarization, effector molecule secretion, autophagy, killing, and survival. The direction of these CCL2-induced responses is context dependent and, in some cases, synergistic with other inflammatory stimuli. The involvement of CCL2 signaling in multiple diseases renders it an interesting therapeutic target, although current targeting strategies have not met early expectations in the clinic. A better understanding of how CCL2 affects immune cells will be pivotal to the improvement of existing therapeutic approaches and the development of new drugs. Here, we provide an overview of the pleiotropic effects of CCL2 signaling on cells of the myeloid lineage, beyond chemotaxis, and highlight how these actions might help to shape immune cell behavior and tumor immunity.

Molecular tracking devices quantify antigen distribution and archiving in the lymph node

“…(consistent with active recruitment of inflammatory cells 66,69 ), Msr1 (consistent with antigen scavenging 71 ), as well as Pkm, Galectin 3, and Mif (consistent with DC-T cell responses and DC differentiation during inflammation 63,65,68 ) ( Fig. 4c,d).…”

“…4a,b). To validate this approach, we evaluated the dendritic cell populations, as genes associated with phagocytosis and activation have been established 50,63,64,65,66,67,68,69,70,71,72 . Dendritic cell populations generally contained lower antigen levels that were variable across subtype (Fig 3).…”

Complex Tissue Regeneration in Mammals Is Associated With Reduced Inflammatory Cytokines and an Influx of T Cells

“…While unique macrophage phenotype may exist in spiny mice, it is equally plausible that the unique combination of cytokines expressed in the evolving wound environment create macrophage population dynamics that are specific to regeneration or fibrotic repair. For instance, CCL2 is a potent macrophage driver that can act singly or synergistically to polarize macrophages and affect production of secreted products [reviewed in (81)]. Resolving which specific macrophage populations are present, and how they behave during regeneration and fibrotic repair, will require single-cell approaches and thus awaits further exploration.…”

Immunomodulation and Immune Escape Strategies of Gastrointestinal Helminths and Schistosomes

“…CX3CL1 does have a chemoattracting effect on monocytes, NK cells and T cells (66). CCL2 is mainly driving chemotaxis of monocytes, but also other cell types, and can regulate further mechanisms, like cytokine secretion or cell adhesion (67). Since CCL3 and CCL5 do have chemotactic properties as well, it is clear that smCKBP targets mainly chemotaxis of immune cells which are for example involved in building the granuloma.…”