Figure 7.

GPR183 supports the early stages of monocyte-to-lung macrophage differentiation, and GPR183 ligand produced by non-hematopoietic cells is required for monocyte-to-lung macrophage differentiation. (A and B) Chimerism of donor-derived monocytes and macrophages in bone marrow, blood, and lung of competitive Gpr183+/+/Gpr183−/− chimeras 3 wk after bone marrow transfer. Gating strategy is shown in Fig. S1 B. The ratio of the indicated Gpr183+/+/Gpr183−/− cells was normalized to the bone marrow input of each independent chimera experiment. AMs, alveolar macrophages; BM, bone marrow; mono-mac, monocyte-macrophages; monos, monocytes. Data are represented as mean ± SEM. ns, not significant; **P < 0.01; ***P < 0.001; ****P < 0.0001 by one-way ANOVA with Tukey’s multiple comparison post hoc test (upper graph in panel B) or by unpaired Student’s t test (lower graph in panel B). Data are pooled from three (Ly6Chi monocytes in bone marrow and blood) or four (monocytes and macrophages in lung) independent bone marrow chimera experiments with a total of n = 8–13 mice per genotype. (C) Chimerism of alveolar and interstitial macrophages in the indicated Gpr183+/+/B6 or Gpr183−/−/B6 → Ch25h+/+ or Ch25h−/− bone marrow chimeras 7–15 wk after bone marrow transfer. Gating strategy is shown in Fig. S1 C. The ratio of the indicated Gpr183+/+/B6 or Gpr183−/−/B6 cells was normalized to the bone marrow input of each independent chimera experiment. Data are represented as mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 by one-way ANOVA with Tukey’s multiple comparison post hoc test. Data are pooled from two independent bone marrow chimera experiments with a total of n = 7–14 mice per genotype. (D)Ch25h mRNA expression in the lung of the indicated chimeras 3–4 wk after bone marrow transfer. Data are represented as mean ± SEM. **P < 0.01; ***P < 0.001; ****P < 0.0001 by one-way ANOVA with Tukey’s multiple comparison post hoc test. Data are pooled from four independent bone marrow chimera experiments with a total of n = 8–12 mice per genotype. Panels A, C, and D were adapted from Servier Medical Art.

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