Alternatively activated macrophages; a double-edged sword in allergic asthma

Table 1 M2 subsets of macrophages, inducing stimuli, significant markers and functions

M2 subtype	Inducing stimuli	Signature markers	Functions	References
M2a^a	IL-4, IL-13 and M-CSF	CD206, Arg1, Ym1, FIZZ1 IL-10, TGF-β	Anti-inflammatory and Wound healing	[4, 6,7,8]
M2b	TLR ligands + IL-1R agonist	CD206, IL-1 β, IL-6, TNF-α, IL-12^Low IL-10	Immuno-regulation and promoting infections
M2c	IL-10, Glucocorticoids, TGF-β	CD206, CD163, MerTK IL-10, TGF- β	Efferocytosis and tissue remodeling
M2d	TLR + adenosine A2A R ligands, IL-6	VEGF, IL-10 TGF- β IL-12^Low, TNF-α^Low	Angiogenesis, Tumor growth

^aM2a macrophage is induced by IL-4 and IL-13, expressing high CD206, Arg1, Ym1, FIZZ1 and TGF-β, promoting fibrosis and wound healing, so called wound healing macrophage. M2b is stimulated by exposure to both immune complex and Toll like receptor (TLR) ligand or IL-1 receptor agonist. M2b is the only subtype that secrets proinflammatory cytokines; IL-1β, IL-6 and TNF-α, however it secrets low IL-12 (So not inducing Th1) and high anti-inflammatory IL-10, thus, performing some immunoregulatory functions. M2c is induced by IL-10, glucocorticoids and TGF-β, expressing high levels of innate receptors CD206, CD163 and the Mer receptor tyrosine kinase (MerTK) which enable it to perform efferocytosis function (phagocytic clearance of dead cells). M2d is induced by combined exposure to TLR with adenosine A2A receptor ligands, or by IL-6, expressing high vascular endothelial growth factor (VEGF) and IL-10, enabling it to induce angiogenesis and promote tumor growth

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