On the role of DNA methyltransferase 3A (DNMT3A) in myeloid cells in intestinal homeostasis and inflammatory responses

This thesis investigates the role of DNMT3A (a de novo methyltransferase), in intestinal homeostasis and during inflammation. This research shows that Dnmt3a is key in maintaining mucosal permeability, and that its lack compromises intestinal epithelial cells ability of regeneration and tissue repair, hence, hijacking tissue integrity. Also, we show that Dnmt3a is crucial for macrophage polarization and effector functions, as its depletion favors a proinflammatory phenotype. Thus, genetic disturbances in DNMT3A gene could provoke a decreased threshold for developing an exacerbated proinflammatory immune response in inflammatory bowel disease patients. In summary, we could postulate Dnmt3a to be essential for tissue integrity and mucosal permeability in the intestinal epithelium, and that it is central in tuning macrophages polarization in response to detrimental insults in an age-dependent manner.

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