In summary, our study demonstrates that MANF restricts the recruitment of Ly6ChiCX3CR1int proinflammatory macrophages to colon tissue and promotes tissue repair in DSS-induced colitis by inhibiting CHOP-BATF2 signaling pathway via BATF2-mediated innate immune pathway and Th17-dominated adaptive immune responses, respectively (Fig. 8). Here, MANF is linked to colitis.