Fig. 4: Therapeutic treatment of acute myocarditis in TCRM mice with anti-GREM 1/2 monoclonal antibody (14-D10-2).

a, Schematic representation of the experimental design. b, Enumeration of CD45⁺ heart-infiltrating cells in 8-week-old TCRM mice treated with IgG2b isotype control or GREM1/2-neutralizing antibody (14-D10-2) using flow cytometry. c, Representative confocal microscopy images showing collagen deposition and immune infiltrates in the hearts of TCRM mice treated with isotype or 14-D10-2 antibodies. d,e, Flow cytometry-based enumeration (d) and functional characterization (e) of MYH6-specific, Vα2⁺Vβ8⁺CD4⁺ T cells with representative dot plots (left) and quantification of cytokine-producing MYH6-specific T cells (right). f–h, Flow cytometric enumeration of CD11b⁺Ly6C⁺CCR2⁺ inflammatory monocytes (f), CD11b⁺Ly6C^intLy6G⁺ neutrophils (g) and CD11b⁺CD64⁺MHCII^hi activated macrophages (h). i, MFI of CD86 expression on CD11b⁺CD64⁺MHCII^hi activated macrophages. j, Tnf mRNA expression by sorted CD11b⁺Ly6G⁻ myeloid cells. k, IL-1β protein concentration in cardiac homogenates. l, Fraction of CD157⁺SCA1⁺ cells of CD45⁻PDPN⁺CD31⁻ cardiac fibroblasts. m, MFI of the indicated activation markers by CD45⁻PDPN⁺CD31⁻ cardiac fibroblasts. n, Representative confocal microscopy images showing BMP4 production by CD34⁺ fibroblasts in inflamed hearts of isotype antibody-treated TCRM mice and restoration of BMP4 production by 14-D10-2 antibody treatment. o, Quantification of BMP4 protein in heart homogenates by ELISA. Box plots as in Fig.1; pooled data from three independent experiments with n = 6 (control) or n = 9 (TCRM) mice per group (b,d–m,o). Representative sections from one out of five control or TCRM mice (c,n). Statistical analysis was performed using Student’s t-test with *P < 0.05, **P < 0.01 and ***P < 0.001.

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