Another way to classify the function and phenotype of M2 cells is based on the cytokines that induce them. The prototypical cytokine used to first induce alternative activation was IL-4 [8]. Both IL-4 and the closely related cytokine IL-13 signal through IL-4Rα to induce a host of downstream processes that lead to potent anti-inflammatory functions, such as Arg1 upregulation, inhibition of NF-κB isoforms, and production of scavenger receptors for phagocytosis [19,47,48]. This type of activation has been classified as ‘M2a’. The main function of this response appears to be suppression of inflammation. A second state of alternative activation is based on macrophages exposed to IL-10, glucocorticoids, or TGF-β. This phenotype is classified as ‘M2c’ [21,49]. Originally, this state was described as being ‘deactivated’ but that is not a particularly useful description. Instead of having no function, ‘deactivated’ M2c macrophages appear to be involved in tissue remodeling and matrix deposition after inflammation has been downregulated [21]. A third sub-class of M2 activation has been observed following exposure to immune complexes and stimulation of TLR. This class is termed ‘M2b’ or Type
