Regulatory macrophages (Mregs) represent a subset of anti-inflammatory macrophages. In general, macrophages are a very dynamic and plastic cell type and can be divided into two main groups: classically activated macrophages (M1) and alternatively activated macrophages (M2). M2 group can further be divided into sub-groups M2a, M2b, M2c, and M2d. Typically the M2 cells have anti-inflammatory and regulatory properties and produce many different anti-inflammatory

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...

s such as IL-4,

IL-33 Interleukin 33 (IL-33) is a protein that in humans is encoded by the ''IL33'' gene. Interleukin 33 is a member of the IL-1 family that potently drives production of T helper-2 (Th2)-associated cytokines (e.g., IL-4). IL33 is a ligand for ST2 ...

, IL-10,

IL-1RA The interleukin-1 receptor antagonist protein (IL-1RN) is a protein that in humans is encoded by the ''IL1RN'' gene. IL-1RN was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories. IL-1RN is a ...

, and

TGF-β Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other ...

. M2 cells can also secrete

angiogenic Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...

and chemotactic factors. These cells can be distinguished based on the different expression levels of various surface proteins and the secretion of different effector molecules. M2a, mainly known as alternatively activated macrophages, are macrophages associated with tissue healing due to the production of components of

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide struc ...

. M2a cells are induced by IL-4 and IL-13. M2b, generally referred to as regulatory macrophages (Mregs), are characterized by secreting large amounts of IL-10 and small amounts of IL-12. M2c, also known as deactivated macrophages, secrete large amounts of IL-10 and

. M2c are induced by

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verte ...

s and

. M2d are pro-angiogenic cells that secrete IL-10,

, and

vascular endothelial growth factor Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, ...

and are induced by IL-6 and A2 adenosine receptor agonist (A2R).

Mreg origin and induction

Mregs can arise following

innate {{Short pages monitor