Background
Methods
RT and Pamrevlumab administration
Expression analysis
Results
Pamrevlumab normalizes RT-induced gene expression changes
Many RT and pamrevlumab response genes are immune cell related
Enrichment of mesenchymal and immune cell distinguishing genes in RT-injured lungs
Cell Type | (n, N) | Fold Enrichment |
p
|
---|---|---|---|
Macrophage | (98, 123) | 14.2 | 3E-148 |
Dendritic Cell | (26, 45) | 10.3 | 6E-32 |
Mesenchymal Cell | (28, 73) | 6.8 | 1E-23 |
Mast Cell | (42, 149) | 5.0 | 8E-25 |
Neutrophil | (14, 49) | 3.3 | 2E-05 |
B Cell | (11, 81) | 2.4 | 0.005 |
Endothelial Cell | (9, 43) | 2.4 | 0.012 |
T Cell | (7, 81) | 1.5 | 0.27 |
Epithelial Cell (Lung) | (10, 91) | 1.3 | 0.46 |
Epithelial Cell (Retina) | (2, 115) | 0.31 | 0.08 |
18w Fc vs noRT | 30w Fc vs noRT | ||||
---|---|---|---|---|---|
Gene ID | Description | RT | RT + FG | RT | RT + FG |
Mast Cell | |||||
Mcpt4 | mast cell protease 4 | 109.9 | 5.9 | 10.7 | 2.2 |
Cpa3 | carboxypeptidase A3, mast cell | 94.2 | 3.3 | 19.9 | 3.0 |
Cma2 | chymase 2, mast cell protease 9 | 51.6 | 3.6 | 9.0 | 2.0 |
Cma1 | chymase 1, mast cell | 46.5 | 2.7 | 4.8 | 1.1 |
Tpsg1 | tryptase gamma 1, mast cell protease 2 | 22.7 | 2.7 | 40.2 | 5.0 |
Mrgprb1 | MAS-related GPR, member B1 | 20.3 | 2.9 | 8.5 | 1.7 |
Darc | Duffy blood group, chemokine receptor | 18.5 | 1.9 | 2.3 | 0.9 |
Tpsb2 | tryptase beta 2, mast cell protease 6 | 18.0 | 2.5 | 5.5 | 3.8 |
Macrophage | |||||
Mmp12 | matrix metallopeptidase 12 | 24.0 | 0.4 | 6.0 | 1.2 |
Trem2 | triggering receptor expressed on myeloid cells 2 | 15.5 | 1.4 | 7.0 | 1.6 |
Msr1 | macrophage scavenger receptor 1 | 10.0 | 0.5 | 5.1 | 1.2 |
Cd200r1 | CD200 receptor 1 | 7.1 | 1.0 | 3.1 | 1.1 |
Ccl3 | chemokine ligand 3 | 6.9 | 0.8 | 1.3 | 0.4 |
Ms4a7 | membrane-spanning 4-domains, subfamily A, member 7 | 6.8 | 1.0 | 2.5 | 0.9 |
Fcgr2b | Fc receptor, IgG, low affinity IIb | 6.6 | 0.7 | 2.2 | 1.3 |
Ms4a6d | membrane-spanning 4-domains, subfamily A, member 6D | 6.5 | 0.4 | 2.4 | 1.2 |
Dendritic Cell | |||||
Cxcl9 | chemokine (C-X-C motif) ligand 9 | 79.8 | 4.0 | 1.1 | 0.5 |
Kynu | kynureninase | 6.5 | 0.8 | 2.3 | 1.3 |
Dnase1l3 | deoxyribonuclease 1-like 3 | 5.6 | 2.5 | 0.9 | 1.0 |
Serpina3g | serine peptidase inhibitor, clade A, member 3G | 5.3 | 1.1 | 1.6 | 1.1 |
Ppfia4 | protein tyrosine phosphatase, f polypeptide, interacting, a4 | 5.1 | 1.3 | 2.5 | 1.3 |
Ffar2 | free fatty acid receptor 2 | 4.1 | 1.8 | 1.8 | 0.9 |
Itgax | integrin alpha X | 4.1 | 0.7 | 1.9 | 0.8 |
Ccl5 | chemokine (C-C motif) ligand 5 | 3.9 | 1.7 | 0.9 | 0.8 |
Mesenchymal Cell | |||||
Dlk1 | delta-like 1 homolog (Drosophila) | 15.2 | 4.7 | 26.3 | 10.4 |
Timp1 | tissue inhibitor of metalloproteinase 1 | 8.2 | 0.4 | 3.6 | 0.8 |
Fn1 | fibronectin 1 | 7.4 | 1.3 | 3.9 | 1.7 |
Wisp1 | WNT1 inducible signaling pathway protein 1 | 5.3 | 0.9 | 2.4 | 1.5 |
Ptx3 | pentraxin related gene | 4.7 | 1.1 | 1.6 | 1.2 |
Col5a2 | collagen, type V, alpha 2 | 4.5 | 0.6 | 1.7 | 1.1 |
Wisp2 | WNT1 inducible signaling pathway protein 2 | 4.0 | 0.9 | 2.7 | 1.3 |
Fstl1 | follistatin-like 1 | 4.0 | 1.0 | 2.4 | 1.3 |
Neutrophil | |||||
Clec7a | C-type lectin domain family 7, member a | 6.0 | 0.7 | 1.5 | 0.6 |
Aif1 | allograft inflammatory factor 1 | 4.1 | 1.1 | 2.0 | 1.1 |
Ffar2 | free fatty acid receptor 2 | 4.1 | 1.8 | 1.8 | 0.9 |
P2ry13 | purinergic receptor P2Y, G-protein coupled 13 | 2.7 | 0.4 | 1.3 | 0.9 |
Fpr1 | formyl peptide receptor 1 | 2.4 | 0.7 | 1.6 | 0.8 |
Lst1 | leukocyte specific transcript 1 | 2.3 | 0.8 | 1.1 | 0.8 |
Mnda | myeloid cell nuclear differentiation antigen | 2.1 | 1.5 | 1.5 | 1.1 |
B-cell | |||||
Igl-V1 | immunoglobulin lambda chain (IgL) mRNA | 8.0 | 1.2 | 0.7 | 1.4 |
March1 | membrane-associated ring finger (C3HC4) 1 | 3.3 | 1.1 | 1.7 | 1.3 |
Ulbp1 | UL16 binding protein 1 | 3.3 | 0.7 | 1.8 | 1.3 |
Cd22 | CD22 antigen | 3.0 | 2.4 | 1.3 | 1.3 |
H2-DMb2 | histocompatibility 2, class II, locus Mb2 | 2.8 | 1.1 | 0.9 | 1.3 |
Tlr1 | toll-like receptor 1 | 2.7 | 1.0 | 1.1 | 1.1 |
Mef2c | myocyte enhancer factor 2C | 2.2 | 1.7 | 1.5 | 0.9 |
Endothelial Cell | |||||
Col4a1 | collagen, type IV, alpha 1 | 3.20 | 0.6 | 1.82 | 1.2 |
Col4a2 | collagen, type IV, alpha 2 | 3.11 | 0.5 | 1.76 | 1.2 |
Fabp4 | fatty acid binding protein 4, adipocyte | 3.01 | 1.2 | 1.73 | 0.5 |
Mgp | matrix Gla protein | 2.07 | 0.7 | 1.39 | 1.1 |
Multiple Potential Cell Sources | |||||
Ankrd34b | ankyrin repeat domain 34B | 224.3 | 8.9 | 8.9 | 1.1 |
Chl1 | cell adhesion molecule with homology to L1CAM | 93.8 | 1.3 | 15.6 | 1.0 |
Ucma | upper zone of growth plate and cartilage matrix associated | 71.2 | 1.8 | 9.9 | 1.2 |
Tnfsf18 | tumor necrosis factor (ligand) superfamily, member 18 | 46.8 | 3.6 | 2.8 | 1.0 |
Gdf3 | growth differentiation factor 3 | 32.1 | 3.9 | 4.2 | 1.1 |
Ear5 | eosinophil-associated, ribonuclease A family, member 5 | 29.5 | 2.1 | 18.3 | 1.6 |
Ccl8 | chemokine (C-C motif) ligand 8 | 29.0 | 2.0 | 5.4 | 0.9 |
Dio3 | deiodinase, iodothyronine type III | 25.6 | 1.4 | 10.3 | 1.1 |
18w Fc vs noRT | 30w Fc vs noRT | ||||
---|---|---|---|---|---|
Gene ID | Description | RT | RT + FG | RT | RT + FG |
Chemokines (Chemotaxis) | |||||
Cxcl9 | chemokine (C-X-C motif) ligand 9 | 79.8 | 4.0 | 1.1 | 0.5 |
Ccl8 | chemokine (C-C motif) ligand 8 (MCP-2) | 29.0 | 2.0 | 5.4 | 0.9 |
Cxcl10 | chemokine (C-X-C motif) ligand 10 | 17.2 | 1.5 | 1.0 | 0.5 |
Ccl1 | chemokine (C-C motif) ligand 1 | 8.9 | 2.1 | 2.9 | 1.2 |
Ccl12 | chemokine (C-C motif) ligand 12 (MCP-5) | 8.3 | 0.6 | 1.9 | 0.7 |
Ccl7 | chemokine (C-C motif) ligand 7 (MCP-3) | 7.9 | 0.6 | 1.3 | 0.5 |
Ccl2 | chemokine (C-C motif) ligand 2 (MCP-1) | 7.3 | 0.6 | 1.1 | 0.5 |
Ccl3 | chemokine (C-C motif) ligand 3 (MIP-1a) | 6.9 | 0.8 | 1.3 | 0.4 |
Ccl6 | chemokine (C-C motif) ligand 6 | 5.8 | 0.7 | 2.8 | 1.1 |
Ccl9 | chemokine (C-C motif) ligand 9 (MIP-1 g) | 5.7 | 0.8 | 2.2 | 1.0 |
Ccl5 | chemokine (C-C motif) ligand 5 (RANTES) | 3.9 | 1.7 | 0.9 | 0.8 |
Ccl17 | chemokine (C-C motif) ligand 17 | 3.7 | 1.1 | 0.9 | 0.7 |
Ccl4 | chemokine (C-C motif) ligand 4 (MIP-1 p) | 3.6 | 1.4 | 0.9 | 0.6 |
Cxcl1 | chemokine (C-X-C motif) ligand 1 | 2.4 | 0.6 | 0.7 | 0.5 |
Cxcl16 | chemokine (C-X-C motif) ligand 16 | 2.3 | 0.7 | 1.4 | 0.9 |
Cxcl12 | chemokine (C-X-C motif) ligand 12 (SDF-1) | 2.2 | 0.5 | 1.4 | 1.1 |
Cxcl3 | chemokine (C-X-C motif) ligand 3 (MIP-2p) | 2.0 | 0.5 | 2.2 | 0.7 |
Cytokines (Cell Activation) | |||||
Tnfsf18 | tumor necrosis factor (ligand) superfamily, member 18 | 46.8 | 3.6 | 2.8 | 1.0 |
Il1rn | interleukin 1 receptor antagonist | 5.7 | 1.2 | 1.8 | 0.7 |
Il6 | interleukin 6 | 4.7 | 1.0 | 1.7 | 0.6 |
Il12b | interleukin 12b | 4.7 | 1.6 | 0.9 | 0.8 |
Tnfsf8 | tumor necrosis factor (ligand) superfamily, member 8 | 4.4 | 1.6 | 1.9 | 1.1 |
C1qtnf9 | C1q and tumor necrosis factor related protein 9 | 3.8 | 1.7 | 2.6 | 1.2 |
C1qtnf5 | C1q and tumor necrosis factor related protein 5 | 2.5 | 1.0 | 1.7 | 1.2 |
Il18 | interleukin 18 | 2.4 | 0.6 | 1.6 | 1.0 |
Il4 | interleukin 4 | 2.4 | 1.7 | 0.9 | 0.7 |
Il12a | interleukin 12a | 0.5 | 1.1 | 0.6 | 1.4 |
TGFβ / BMP Signaling (Differentiation, Migration, ECM Production,...) | |||||
Gdf3 | growth differentiation factor 3 | 32.1 | 3.9 | 4.2 | 1.1 |
Inhba | inhibin beta-A | 7.8 | 1.1 | 1.9 | 1.2 |
Gdf6 | growth differentiation factor 6 (BMP13) | 5.9 | 0.6 | 3.7 | 1.8 |
Fst | follistatin | 5.7 | 0.8 | 1.5 | 1.1 |
Grem1 | gremlin 1 | 4.7 | 1.8 | 1.5 | 0.8 |
Gdf15 | growth differentiation factor 15 | 4.0 | 1.7 | 3.0 | 2.6 |
Fstl1 | follistatin-like 1 | 4.0 | 1.0 | 2.4 | 1.3 |
Ltbp2 | latent transforming growth factor beta binding protein 2 | 3.9 | 1.0 | 2.1 | 1.3 |
Ctgf | connective tissue growth factor | 3.5 | 1.1 | 1.2 | 0.8 |
Bmp8a | bone morphogenetic protein 8a | 2.8 | 1.2 | 1.9 | 1.5 |
Bmp6 | bone morphogenetic protein 6 | 0.2 | 0.3 | 0.4 | 0.7 |
Wnt Signaling (Cell Polarity, Pattern Formation) | |||||
Wnt10a | wingless related MMTV integration site 10a | 22.1 | 1.1 | 2.3 | 1.1 |
Frzb | frizzled-related protein | 8.5 | 1.2 | 2.2 | 0.9 |
Sfrp1 | secreted frizzled-related protein 1 | 6.3 | 0.6 | 3.2 | 1.0 |
Wisp1 | WNT1 inducible signaling pathway protein 1 | 5.3 | 0.9 | 2.4 | 1.5 |
Wisp2 | WNT1 inducible signaling pathway protein 2 | 4.0 | 0.9 | 2.7 | 1.3 |
Fzd2 | frizzled homolog 2 (Drosophila) | 2.8 | 0.9 | 1.8 | 1.2 |
Wnt7a | wingless-related MMTV integration site 7A | 2.7 | 1.2 | 1.3 | 0.9 |
Fzd7 | frizzled homolog 7 (Drosophila) | 2.0 | 0.8 | 1.5 | 0.8 |
IGF Signaling (Proliferation, Survival) | |||||
Insl6 | insulin-like 6 | 7.9 | 1.4 | 3.1 | 1.2 |
Igf1 | insulin-like growth factor 1 | 6.3 | 0.7 | 4.7 | 1.3 |
Igfbp2 | insulin-like growth factor binding protein 2 | 3.5 | 0.8 | 1.9 | 1.6 |
Igfbp4 | insulin-like growth factor binding protein 4 | 2.6 | 1.4 | 1.5 | 1.1 |
Igfbp7 | insulin-like growth factor binding protein 7 | 2.5 | 0.7 | 1.5 | 1.2 |
Igfbp6 | insulin-like growth factor binding protein 6 | 0.3 | 0.6 | 0.6 | 0.9 |
Other Cytokines & Growth Factors | |||||
Retnla | resistin like alpha | 10.5 | 1.7 | 6.4 | 1.4 |
Angptl7 | angiopoietin-like 7 | 5.0 | 1.4 | 1.0 | 1.0 |
Pdgfc | platelet-derived growth factor, C polypeptide | 4.2 | 0.4 | 1.5 | 1.0 |
Csf3 | colony stimulating factor 3 (G-CSF) | 3.3 | 2.3 | 1.4 | 1.1 |
Angptl3 | angiopoietin-like 3 | 3.2 | 1.2 | 1.8 | 1.3 |
Fgf2 | fibroblast growth factor 2 | 2.5 | 1.3 | 1.4 | 0.9 |
Pdgfd | platelet-derived growth factor, D polypeptide | 2.2 | 0.9 | 1.9 | 1.4 |
Pgf | placental growth factor | 2.1 | 0.9 | 1.1 | 0.8 |
Fgfbp1 | fibroblast growth factor binding protein 1 | 0.4 | 0.6 | 0.7 | 1.1 |
Cytl1 | cytokine-like 1 | 0.3 | 1.0 | 0.4 | 0.7 |
Retn | resistin | 0.2 | 1.2 | 0.2 | 0.3 |