Treg in cardiomyocyte regeneration. Treg is crucial in the repair of myocardium post-MI in both adult and neonatal mice. One mechanism proposed is the modulation of M2 macrophages, which promote the formation of scar tissue after MI. However, perhaps due to the different subtypes of M2 macrophages identified in neonatal and adult mice in the myocardium, Treg promotes the expression of M2 cytokines by M2 macrophages in adults but suppresses them in neonatal mice post-MI. Another mechanism of promoting myocardium repair is through the production of adenosine from CD39 expressed on Treg cell surface, and adenosine protects cardiomyocytes from apoptosis by activating RISK pathway. Treg can also directly influence the proliferation of cardiomyocytes in neonates and adults after MI. Even though adult cardiomyocytes do not possess inherent regeneration potential unlike neonatal cardiomyocytes, after MI, Treg promotes the proliferation of cardiomyocytes despite the mechanism remains unknown. Several paracrine factors released by Treg have been identified to promote neonatal cardiomyocytes proliferation, and they include CCL24, GAS7, AREG, CSR7, TNFSF11, IL33, FGL2, MATN2, and IGF2.