[80] Classical DCs share a number of common features and functions with macrophages. Traditionally, it was thought that blood monocytes harness the potential to give rise to classical DCs once recruited into surrounding tissues.[16, 81, 82] However, this notion has recently been superseded with the discovery that DCs originate from the bone marrow precursor, MDP, which also gives rise to monocytes and several subsets of macrophages (Fig. 2).[83] In fact, DCs develop exclusively from MDPs via an alternative precursor population known as the common DC precursor (CDP). CH5424802 chemical structure This precursor also differentiates

into plasmacytoid DCs and the precursors for classical DCs.[84-86] Despite these discoveries, c-Met inhibitor studies still support the conclusion that monocytes can differentiate into DCs following

injury. A subpopulation of DCs, termed inflammatory DCs, are able to differentiate from inflammatory Ly6Chi monocytes and share common features with macrophages in non-lymphoid organs such as in the intestine,[87, 88] lung,[89] skin[90] and kidney.[67, 91-93] Given these similarities in ontogeny and function between DC subpopulations and macrophages, there is significant confusion and controversy when defining and distinguishing between them, particularly in non-lymphoid organs.[78] The concept that macrophages and DCs represent two functional extremes of a continuum of progeny of the CMP stems from their redundancy in molecular marker expression, function and location in the kidney and other non-lymphoid organs of the body.[94] Nonetheless, a characteristic feature defining cells of

the mononuclear phagocyte system is their CSF-1 receptor (CSF-1R) expression.[95] CSF-1 essentially drives the differentiation and expansion of monocytes and macrophages from bone marrow precursors by binding to the CSF-1R. This receptor is expressed on all cells of the mononuclear phagocyte system, including all DC subsets.[96, 97] MacDonald et al.[96] observed that DC populations are significantly reduced in CSF-1-deficient mice, thus highlighting that CSF-1 signalling is imperative for the optimal differentiation of DCs in check details vivo. Dendritic cells share a number of molecular markers with macrophages.[98] These molecular markers include the DC marker CD11c, the macrophage markers CD11b and F4/80, costimulatory and MHC molecules, and the CSF-1R and CX3CR1. Despite their heterogeneity, all DC subsets express the integrin CD11c in mice and humans, but with less specificity in humans.[99] As a result, CD11c expression has been widely used in numerous studies to distinguish between DCs and macrophages.[100] However, CD11c is expressed on a large population of mouse and human macrophages in almost every organ of the body including the kidney.