Regulation of Type 2 Immunity in Myocardial Infarction

Abstract

Type 2 immunity participates in the pathogeneses of helminth infection and allergic diseases. Emerging evidence indicates that the components of type 2 immunity are also involved in maintaining metabolic hemostasis and facilitating the healing process after tissue injury. Numerous preclinical studies have suggested regulation of type 2 immunity-related cytokines, such as interleukin-4, -13, and -33, and cell types, such as M2 macrophages, mast cells, and eosinophils, affects cardiac functions after myocardial infarction (MI), providing new insights into the importance of immune modulation in the infarcted heart. This review provides an overview of the functions of these cytokines and cells in the setting of MI as well as their potential to predict the severity and prognosis of MI.

Keywords: M2 macrophages; eosinophils; immune modulation; interleukin; mast cells; myocardial infarction; type 2 immunity.

Figure 1

Functions of M2 macrophages, mast cells, and eosinophils in MI.

Figure 2

After myocardial ischemic attack, resident cardiac macrophages begin to develop apoptose by 2 h and circulating monocytes infiltrate into the injury site and differentiate into macrophages. Elicited by IL-4 and IL-13, macrophages polarize toward the M2 phenotype through activation of STAT6. M2 macrophages facilitate the recovery of cardiac functions via secretion of anti-inflammatory cytokines, promoting angiogenesis and collagen deposition.

Figure 3

Mechanisms of macrophage polarization after MI.

Figure 4

In the setting of MI, the diverse biological effects of mast cells are largely mediated by their granules containing renin, chymase, tryptase, and TNF-α. Degranulation of mast cells induces activation of local RAS, inflammatory cell recruitment, angiogenesis, and regulation of cardiomyocyte contractility and apoptosis.