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. Author manuscript; available in PMC: 2019 Jun 5.
Published in final edited form as: Circulation. 2018 Jan 31;137(23):2478–2493. doi: 10.1161/CIRCULATIONAHA.117.033144

Figure 8. A summary working model for the initiation of cardiac valve inflammation and fibrosis in K/B.g7 mice.

Figure 8

Anti-glucose-6-phosphate isomerase (α-GPI) IgG auto-antibodies produced systemically in the secondary lymphoid tissue (spleen and lymph nodes) (1) activate valve-infiltrating mononuclear phagocytes (MNPs) in a spleen tyrosine kinase (Syk)-dependent process (2) resulting in local production of TNF and IL-6 from CX3CR1+CD301b/MGL2+ MNPs. Tumor necrosis factor receptor-1 (TNFR1)-mediated activation of the valve stroma (3) promotes vascular cell adhesion molecule-1 (VCAM-1) upregulation (4) and subsequent recruitment of additional circulating CX3CR1+ MNPs via very-late antigen-4 (VLA-4, α4β1 integrin) in a feed-forward process (5). Interstitial MNPs assume a tissue-reparative phenotype characterized by expression of CD301b/MGL2, resistin-like molecule-alpha (RELM-α), and arginase-1 (Arg-1) (6). Explanation of terms: KRN TCR: transgenic T cell receptor; I-Ag7 MHC-II: major histocompatibility complex-II from the non-obese diabetic (NOD) mouse strain; APC: antigen presenting cell (e.g. dendritic cells); MGL2: macrophage galactose N-acetyl-galactosamine specific lectin 2.