| It was usually thought that the major function of immune cells is dealing with conditions of infection,injury and tumor,etc,in which the immune cells are crucial in both protection and repair.Almost all tissues are distributed with resident immune cells.Recent advances unveiled that besides playing a role as immune responders,resident immune cells are critical in maintaining local homeostasis and normal organ functions.Kidney is the major organ controlling body salt and water balance.The interstitium of kidney involves a variety of components including immune cells.However,the roles of resident immune cells in renal physiology have been barely explored.In this study,we recognized two subsets of resident macrophages in the kidneys of mouse by a fate mapping technique.They are bone marrow-derived macrophages,which constituted the majority of resident renal macrophages,and embryo-derived self-maintaining macrophages(SM-M(?)).The half life of bone marrow-derived macrophages was about 46 days in the kidneys,while the SM-M(?)were long-lived and did not need supplementation from blood in steady state.These two populations of macrophages were distinctive in transcriptome and in distribution.RNA-seq analysis showed that the SM-M(?) were characterized by enriched expression of transcripts involved in neuronal differentiation and excitation,while the bone marrow-derived macrophages relatively highly expressed genes involved in metabolic processes and molecule transportation.In line,confocal microscopy examination disclosed that the renal sympathetic nerves were surrounded with SM-M(?) which dynamically interacted with nerve axons as their pseudopodia continuously extended and retracted along with the nerve fibers.This motion would expedite in response to increased renal sympathetic activity induced by water deprivation.Targeted depletion of the SM-M(?) resulted in reduced sympathetic activities,as manifested by decreased renal norepinephrine level,leading to increased glomerular filtration rate and solute diuresis,which caused salt decompensation and significant weight loss under low-salt diet challenge.These results highlight a local maintaining mechanism for sympathetic nerve activity,and thereby for body salt and water homeostasis,through renal SM-M(?).Moreover,our findings suggest a local regulatory circuit suited for sympathetic nerve activity.Overall,our study provides insights in renal macrophage heterogeneity,addresses a noncanonical role of macrophages in renal physiology for sympathetic tonicity,and expand understanding on local modulation of sympathetic activity. |
