Tissue-specific differentiation of colonic macrophages requires TGFβ receptor-mediated signaling

Intestinal macrophages (m phi) form one of the largest populations of m phi in the body and are vital for the maintenance of gut homeostasis. They have several unique properties and are derived from local differentiation of classical Ly6C(hi) monocytes, but the factors driving this tissue-specific process are not understood. Here we have used global transcriptomic analysis to identify a unique homeostatic signature of mature colonic m phi that is acquired as they differentiate in the mucosa. By comparing the analogous monocyte differentiation process found in the dermis, we identify TGF beta as an indispensable part of monocyte differentiation in the intestine and show that it enables m phi to adapt precisely to the requirements of their environment. Importantly, TGF beta Rsignaling on m phi has a crucial role in regulating the accumulation of monocytes in the mucosa, via mechanisms that are distinct from those used by IL10.