Interest in intestinal mononuclear phagocytes (MPs), both DCs and macrophages (Mφs), has exploded in the recent years. In this Viewpoint we will detail how resident intestinal lamina propria (LP) Mφs possess distinctive properties that reflect adaptation to a unique microenvironment. They play quite different roles in the normal and inflamed mucosa and, as we will show, the existing paradigms of differentiated Mφ subsets and of 'resident' versus 'inflammatory' monocytes based on other tissues may not apply to the gut. Strategies for targeting Mφs as a means of dampening intestinal inflammation will need to take account of these unique characteristics.
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