Fig 1: Pharmacological blockage of Trem1 using mLR12 could significantly alleviate the lymphedema in a mouse tail model.a TREM1 is predominantly expressed by the pro-inflammatory macrophage subpopulation c8. b Changes in the diameter of mouse tail during the treatment using mLR12 (n = 5) or mLR12-scramble peptides as a control (n = 5). Starting from 15 days after the surgery, mice were treated daily by intraperitoneal injection. The diameter of the tail (1 cm distal to the incision) was measured every 3 days for 6 weeks. Tail tissue samples were collected 6 weeks after the surgery for subsequent assays. *P value < 0.05, **P value < 0.01, n.s. not significant, one-tailed t-test. c Images showing the mouse tails following treatment. d H&E staining of the cross-sections of the mouse tails showing reduced subcutaneous tissue edema in the treatment versus the control group. The double-sided arrow indicates the thickness of subcutaneous tissues. e Thickness of the subcutaneous tissues measured based on the H&E staining images. f Sirius red staining showing decreased fibrosis. Collagens were stained in red. Collagen fibers are disarrayed in the fibrosis of the scramble group. g Immunofluorescent staining showing a reduced number of Cd11b+Trem1+ cells in the treatment group (lower panel) versus the control group (upper panel). The arrows indicate the Cd11b+Trem1+ cells. h Proportion of the Cd11b+Trem1+ macrophages in all Cd11b+ cells in the two groups based on the immunofluorescent staining. i Reduced mRNA expression of Cd68 in the mouse tail tissue following the LR12 treatment. j Reduced mRNA expression of Il1b in the mouse tail tissue following the LR12 treatment. k Reduced mRNA expression of Tnf in the mouse tail tissue following the LR12 treatment. In e, h–k, the significant threshold was set to be a P value of the one-tailed t-test < 0.05 (n = 3). In d, e, sections at almost the same level (located 1 cm distal to the surgical site) were used for both groups.