Fig 2: In vivo effects of monocytic EPOR knockout on bone cell precursors. Flow cytometry analysis of (a) preosteoclasts (CD115+) and (b) preosteoblasts (CD11b-Alp+) from the bone marrow of female LysMCreEPORf/f mice and their controls after treatment with either diluent or EPO. n = 8–12 in each group. * p < 0.05 versus diluent. All data are mean ± SEM. p values were calculated by 2-way ANOVA.

Fig 3: ß-Glucan-trained macrophages express relatively low levels of phagocytic cell surface markers. Undifferentiated monocytes (Mo, day 0) or differentiated macrophages (day 7) were collected and stained with antibodies against CD11b, F4/80, MHC II and CD11c and subsequently assessed by flow cytometry. (a) Representative histogram plots showing the expression of the different cell surface markers in undifferentiated Mo (day 0) or day 7 differentiated macrophages initially primed with ß-glucan (black), LPS (grey) or RPMI (white, control). (b) Percentage of positive cells for each of the four markers evaluated in monocytes and differentiated macrophages. Spleen monocytes from five mice were analysed in independent experiments for all makers. Bars and error bars represent average and s.e.m. values, respectively. * and **P-values ?0.05 and 0.01, respectively.

Fig 4: rHC matrix treatment alters bone marrow cell and macrophage response. a Immunohistochemistry analysis and quantification of the number of CD206+ macrophages (per mm2) in the scar, border zone and remote myocardium of MI hearts treated with PBS, rHCI, or rHCIII. CD206, green; DAPI, blue (n = 6–7). b Flow-cytometry analysis for the number of GFP+, GFP+F4/80+, GFP+CD38+, and GFP+CD11b+ cells recruited from the bone marrow to the left ventricle of Cxcr3-EGFP MI mice 2 days after PBS, rHCI, or rHCIII treatment (n = 9–10). P-values were determined by one-way ANOVA using Holm’s multiple comparison. The data are presented as the mean ± SEM. Source data are provided as a Source Data file. For a, b, n indicates the number of mice per group

Fig 5: Antibiotic treatment rescues the spontaneous gut inflammation in Ripk1K612R/K612R mutant mice.a Body weight of 8 weeks-old male Ripk1+/+ mice treated with antibiotics (n = 6) or vehicle (n = 6), and male Ripk1K612R/K612R mice treated with antibiotics (n = 6) or vehicle (n = 6) for 4 weeks. Data are presented as mean ± SEM of n = 6 biologically independent mice. One-way ANOVA with Dunnett’s multiple comparison test. b IL-6 and TNFa level in sera of 8 weeks-old Ripk1+/+ mice treated with antibiotics (n = 7) or vehicle (n = 7), and Ripk1K612R/K612R mice treated with antibiotics (n = 7) or vehicle (n = 7) for 4 weeks. Data are presented as Mean±SEM of n = 7 biologically independent mice. One-way ANOVA with Dunnett’s multiple comparison test. c Representative images of spleens and spleen weight of 8–9 weeks-old Ripk1+/+ mice treated with antibiotics (n = 6) or vehicle (n = 6), and Ripk1K612R/K612R mice treated with antibiotics (n = 6) or vehicle (n = 6) for 4 weeks. Data are presented as Mean±SEM of n = 8 or 7 biologically independent mice. One-way ANOVA with Dunnett’s multiple comparison test. d Representative images of the large intestine and colon length of 8 weeks-old male Ripk1+/+mice treated with antibiotics (n = 4) or vehicle (n = 4), and male Ripk1K612R/K612R mice treated with antibiotics (n = 4) or vehicle (n = 4) for 4 weeks. Data are presented as mean ± SEM of n = 4 biologically independent mice. One-way ANOVA with Dunnett’s multiple comparison test. e Western blotting analysis of RIPK1 protein levels of the colon and spleen from indicated mice treated with antibiotics or vehicle for 4 weeks as in (d). Uncropped blots in the Source Data file. f Haematoxylin & Eosin staining, PAS/AB staining, and immunohistochemical staining of F4/80, GR-1, and Ki67 in the sections of colon from 8-weeks-old Ripk1+/+ mice treated with antibiotics (n = 3) or vehicle (n = 3), and Ripk1K612R/K612R mice treated with antibiotics (n = 3) or vehicle (n = 3) for 4 weeks (Scale bars, 50 µm). g QRT-PCR analysis of cytokine and cFLIP expression in the colon of 8-weeks-old Ripk1+/+mice treated with antibiotics (n = 8 or 6) or vehicle (n = 8), and Ripk1K612R/K612R mice treated with antibiotics (n = 8) or vehicle (n = 8) for 4 weeks. Data are presented as mean ± SEM of n = 8 or 6 biologically independent mice. One-way ANOVA with Dunnett’s multiple comparison test. h The populations of CD45+CD11b+GR-1+ cells in the spleens and bone marrow of 8-weeks-old Ripk1+/+ mice treated with antibiotics (n = 6) or vehicle (n = 6), and Ripk1K612R/K612R mice treated with antibiotics (n = 6) or vehicle (n = 4) for 4 weeks. Dot plot analysis was performed to visualize the percentages of indicated cell populations. Data are presented as mean ± SEM of n = 6 or 4 biologically independent mice. One-way ANOVA with Dunnett’s multiple comparison test.