Cardiac healing after myocardial ischemia depends on the recruitment and local expansion of myeloid cells, particularly macrophages. Here we identify Reg3β as an essential regulator of macrophage trafficking to the damaged heart. Using mass spectrometry-based secretome analysis, we found that dedifferentiating cardiomyocytes release Reg3β in response to the cytokine OSM, which signals through Jak1 and Stat3. Loss of Reg3β led to a large decrease in the number of macrophages in the ischemic heart, accompanied by increased ventricular dilatation and insufficient removal of neutrophils. This defect in neutrophil removal in turn caused enhanced matrix degradation, delayed collagen deposition and increased susceptibility to cardiac rupture. Our data indicate that OSM, acting through distinct intracellular pathways, regulates both cardiomyocyte dedifferentiation and cardiomyocyte-dependent regulation of macrophage trafficking. Release of OSM from infiltrating neutrophils and macrophages initiates a positive feedback loop in which OSM-induced production of Reg3β in cardiomyocytes attracts additional OSM-secreting macrophages. The activity of the feedback loop controls the degree of macrophage accumulation in the heart, which is instrumental in myocardial healing.

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The aim of the study was to determine the temporal sequence of structural and functional reorganization of hair follicles in the skin of C57BL/6 mice after anagen induction.Material and methods. 30 male mice of the C57BL/6 inbred line were used for the study. Anagen induction was carried out by depilation of the hair shafts of the skin of the back. Mice were withdrawn from the experiment on the 1st, 5th, 9th, 15th, 19th, 28th days after anagen induction. Skin samples of the depilation area were fixed in buffered neutral formalin and examined using survey microscopy, morphometry, immunohistochemistry, and statistics.Results. The study of the morphological picture from the 1st to the 28th day after anagen induction showed that cyclic changes in the thickness of the dermis, subcutaneous adipose tissue and the structure of hair follicles occur in the skin. On the 1st day after anagen induction the synchronous entry of hair follicles into the anagen stage I was observed: hair follicles were completely in the dermis, had a rounded dermal papilla, above which, towards the epidermis, there was a proliferating follicular epithelium in the form of an expanding and elongating strand . On the 5th day, morphological signs corresponding to the stage of anagen III b were observed: hair follicle bulbs were located in the upper third of the subcutaneous tissue. The dermal papillae looked friable and enlarged, around their upper pole there was a zone of melanogenesis, a hair shaft and an internal root epithelial sheath being formed. The morphological changes on the 9th and 15th days corresponded to the anagen stage VI: the tips of the pigmented hair rods emerged from the funnels of the hair follicles to the surface of the epidermis, the hair follicles were located deep in the subcutaneous fatty tissue, reaching the subcutaneous muscle. The hair follicles had a narrow dermal papilla, a zone of melanogenesis, and the forming hair shafts had regular pigmentation. A pronounced thickening of the dermis and subcutaneous adipose tissue was noted. On the 19th day, the hair follicles were in the catagen VI phase: two-row bag-like structures were observed, forming capsules of the secondary hair germ). They surrounded the keratinized brush-like depigmented proximal ends of the hair shafts. Hair follicles with a rounded dermal papilla were located in the middle of the subcutaneous adipose tissue. The dermal papillae were separated from the capsule of the secondary hair germ by a cord of follicular keratinocytes. Proximal to the dermal papillae, elements of the connective tissue sac were visible. On the 28th day, corresponding to the telogen stage, the hair follicles were located completely in the dermis, had a rounded, dense dermal papilla, which was adjacent to the germinal capsule. On the 19th and 28th days after anagen induction, a decrease in the width of the dermis and subcutaneous fat was noted.Conclusions. Thus, during the cycle of the hair follicle, its stage-by-stage remodeling and the change in the thickness of the dermis and subcutaneous fat, dependent on this process, take place. The following time sequence of the structural and functional reorganization of hair follicles was determined: on the 1st day after depilation, the hair follicles were synchronized in the anagen I stage, on the 5th day – anagen IIIb, on the 9th and 15th days – anagen VI, on Day 19 – catagen VI stage, on day 28 – telogen stage.

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