Directly recruited GATA6 + peritoneal cavity macrophages contribute to the repair of intestinal serosal injury

• Published in: Nature communications Vol. 12; no. 1; pp. 7294 - 15
• Main Authors: Honda, Masaki, Kadohisa, Masashi, Yoshii, Daiki, Komohara, Yoshihiro, Hibi, Taizo
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 15.12.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animals; ATP; Bone marrow; CCR2 protein; Colitis; Collagen; Confocal microscopy; CX3CR1 protein; Damage accumulation; Dextran; Dextrans; GATA6 Transcription Factor - genetics; GATA6 Transcription Factor - immunology; Humans; Hyaluronic acid; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - physiopathology; Injuries; Intestine; Intestines - immunology; Macrophages; Macrophages, Peritoneal - immunology; Male; Mice; Mice, Inbred C57BL; Microbiomes; Monocyte chemoattractant protein 1; Monocytes; Monocytes - immunology; Myeloid cells; Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics; Nuclear Receptor Subfamily 4, Group A, Member 1 - immunology; Peritoneum; Peritoneum - immunology; Receptors, CCR2 - genetics; Receptors, CCR2 - immunology; Recruitment; Regeneration; Repair; Sodium sulfate; Thermal injury; Tissue engineering; Tissues
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27614-9

Recruitment of bone marrow derived monocytes via bloodstream and their subsequent conversion to CX3CR1 macrophages in response to intestinal injury is dependent on CCR2, Nr4a1, and the microbiome. This process is critical for proper tissue repair; however, GATA6 peritoneal cavity macrophages might represent an alternative, more readily available source of mature and functional myeloid cells at the damaged intestinal locations. Here we show, using spinning-disk confocal microscopy, that large F4/80 GATA6 peritoneal cavity macrophages promptly accumulate at damaged intestinal sites upon intestinal thermal injury and upon dextran sodium sulfate induced colitis in mice via a direct route from the peritoneal cavity. In contrast to bloodstream derived monocytes/macrophages, cavity macrophages do not depend on CCR2, Nr4a1 or the microbiome for recruitment, but rather on the ATP-release and exposed hyaluronan at the site of injury. They participate in the removal of necrotic cells, revascularization and collagen deposition and thus resolution of tissue damage. In summary, peritoneal cavity macrophages represent a rapid alternative route of intestinal tissue repair to traditional monocyte-derived macrophages.