Abstract
The interstitium of kidney involves a variety of components including resident immune cells, in particular mononuclear phagocytes. However, many proposed markers for distinguishing macrophages or dendritic cells are, in fact, shared by the majority of renal mononuclear phagocytes, which impedes the research of kidney diseases. Here, by employing a flow cytometry strategy and techniques of fate mapping, imaging and lineage depletion, we were able to demarcate renal monocytes, macrophages and dendritic cells and their subsets in mice. In particular, using this strategy, we found that even in steady state, the renal macrophage pool was continuously replenished by bone marrow-derived monocytes in a stepwise process, i.e., from infiltration of classical monocyte, to development of nonclassical monocyte and eventually to differentiation to macrophages. In mechanism, we demonstrated that the ligation of tissue-anchored CX3CL1 and monocytic CX3CR1 was required for promoting monocyte differentiation to macrophages in the kidney, but CX3CL1-CX3CR1 signaling was dispensable in monocyte infiltrating into the kidney. In addition to the bone marrow-derived macrophages, fate mapping in adult mice revealed another population of renal resident macrophages which were embryo-derived and self-maintaining. Thus, the dissecting strategies developed by us would assist in exploration of the biology of renal mononuclear phagocytes.
Highlights
Entrenchment of resident macrophages in most tissues begins during embryogenesis from yolk-sac pro-macrophages and/or fetal liver-derived monocytes [1]
The non-DC identity of SM-MØ is further confirmed by the fact that DCs are derived from the bone marrow (BM) with a high turnover rate [11], so far, only tissue resident macrophage but not DCs in adult mice have been found containing subtypes with embryo origin and self-maintaining
Our findings of kidney were inconsistent with this interstitial macrophage dichotomy in that all renal macrophages are MHC-IIhiCX3CR1hi
Summary
Entrenchment of resident macrophages in most tissues begins during embryogenesis from yolk-sac pro-macrophages and/or fetal liver-derived monocytes [1]. Microglia are exclusively derived from yolk sac and self-renewal can sustain their maintenance and function throughout lives, independent of the adult hematopoiesis [2]. In some organs including gut, heart and lung, the resident macrophage pool is continuously replenished by bone marrow-derived monocytes in adults [1, 3–5], the rate of renewal is widely different across organs. Deriving from the common monocyte progenitors (cMoP) in bone marrow (BM) [6], Ly6Chi classical monocytes are the definitive precursors of many tissue mononuclear phagocytes [7]. They routinely survey steady-state tissues [8] where they can further differentiate to monocyte-derived macrophages. The major emerging challenges are to identify the distinctive subtypes of macrophages in their residing tissues and to understand the mechanisms underlying their establishment in specific tissues
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