Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells

Abstract

Tissue repair is a subset of a broad repertoire of interleukin-4 (IL-4)- and IL-13-dependent host responses during helminth infection. Here we show that IL-4 or IL-13 alone was not sufficient, but IL-4 or IL-13 together with apoptotic cells induced the tissue repair program in macrophages. Genetic ablation of sensors of apoptotic cells impaired the proliferation of tissue-resident macrophages and the induction of anti-inflammatory and tissue repair genes in the lungs after helminth infection or in the gut after induction of colitis. By contrast, the recognition of apoptotic cells was dispensable for cytokine-dependent induction of pattern recognition receptor, cell adhesion, or chemotaxis genes in macrophages. Detection of apoptotic cells can therefore spatially compartmentalize or prevent premature or ectopic activity of pleiotropic, soluble cytokines such as IL-4 or IL-13.

Mechanisms of urodele limb regeneration

“…IL‐4/13‐dependent macrophage proliferation is enhanced by their production of defense collagens (Minutti et al., 2017), and the types of defense collagens produced are dictated by the tissue location of the macrophages. Making this pro‐inflammatory to anti‐inflammatory switch requires that the macrophages first sense apoptotic neutrophils (Bosurgi et al., 2017). The result is “normal” scar formation, but not regeneration.…”

‘Repair’ Treg Cells in Tissue Injury

“…When damage occurs, inflammatory responses are triggered, which subsequently recruit and activate haematopoietic and non-haematopoietic cells that together orchestrate a cellular response to promote tissue repair [1]. Among the immune cells involved in the response to tissue injury, recent findings have expanded our understanding of repair mechanisms by demonstrating new and unexpected roles for some immune cells in repairing damaged tissue according to organ-specific cues [2-5]. Forkhead box P3‑expressing (Foxp3 + ) regulatory T (Treg) cells are a heterogeneous population that are specializes in antagonizing overexuberant immune responses and restoring immune homeostasis [6].…”

Novel Therapeutic Strategies for Solid Tumor Based on Body’s Intrinsic Antitumor Immune System

“…If macrophages could be aroused for targeted phagocytosis of tumor cells, the energy and substances absorbed by tumor cells may be given back to human body, thus achieving a perfect tumor treatment effect. In addition to phagocytosis, macrophages may also play a role in antigen presenting and in the promotion of inflammatory responses, angiogenesis and tissue healing [58][59][60]. Like other immune cells, macrophages have many types of receptors on their surface, including cytokine receptors, scavenger receptors, TLRs, and Fc receptors [61], which may receive different signals and display different functions.…”