Journal: Frontiers in Immunology

Article Title: CD14 + CD16 + monocyte-derived TREM2 macrophages promote lung fibrosis in systemic sclerosis–interstitial lung disease

doi: 10.3389/fimmu.2026.1748574

Figure Lengend Snippet: GM-CSF-induced CD14 + CD16 + monocyte-derived macrophages promoted fibrotic activation of lung fibroblasts, an effect depends upon TREM2 expression. (A) Volcano plot showing DEG in fibroblasts from SScLO compared to those from HCs ( GSE128169 ). Fibrotic activation genes, including POSTN , COL1A1 , COL3A1 , COL4A1 , COL5A1 , COL8A1 , TGFBI , and ACTA2 , were significantly upregulated in SScLO fibroblasts. (B) Schematic diagram of the co-culture experimental design. Monocytes (CD14 + CD16 - or CD14 + CD16 + ) were differentiated into macrophages using GM-CSF for 7 days, then co-cultured with human lung fibroblasts for 5 days with or without TREM2 inhibitor. Bulk RNA sequencing and western blot analyses were performed to assess gene expression and protein levels, respectively. (C) Volcano plots showing DEG in fibroblasts co-cultured with CD14 + CD16 - vs. CD14 + CD16 + macrophages (left) and CD14 + CD16 + macrophages with or without TREM2 inhibitor (right). All macrophages were derived from SSc-ILD patients. Co-culture with CD14 + CD16 + macrophages induced fibrotic gene expression ( POSTN , COL7A1 , ACTA2 , and TGFBI ), which was significantly reduced by TREM2 inhibition. Upregulated genes are shown in red (FC > 2, adj. p < 0.05), downregulated in blue (FC < -2, adj. p < 0.05), and non-significant genes in black. Dotted lines indicate statistical thresholds. (D) Representative western blot images of COL7A1 (34 kDa), COL3A1 (200 kDa), COL1A1 (220 kDa), and α-SMA (42 kDa); GAPDH (37 kDa) was used as a loading control. Conditions with TREM2 inhibitor are indicated in red. (E–H) Quantification of protein levels normalized to GAPDH: (E) COL7A1, (F) COL3A1, (G) COL1A1, and (H) α-SMA. Expression of COL7A1, COL1A1, and α-SMA was significantly elevated in fibroblasts co-cultured with CD14 + CD16 + monocytes derived macrophages from SSc-ILD compared to HCs and CD14 + CD16 - monocytes derived macrophages from SSc-ILD. COL3A1 expression was also elevated in SSc-ILD fibroblasts compared to HCs. TREM2 inhibition markedly reduced expression of all fibrotic markers. Statistical analysis was conducted using MANOVA, followed by Tukey’s post-hoc multiple comparisons test. Data are presented as mean ± SEM, with n = 6 per group. Statistical significance is indicated as * p < 0.05, ** p < 0.01 for comparisons between SSc-ILD and HCs within the same subset; # p < 0.05, ## p < 0.01 for comparisons between CD14 + CD16 - and CD14 + CD16 + subsets within SSc-ILD patients; $ p < 0.05, $$ p < 0.01 for comparisons between SSc-ILD and TREM2 inhibitor within the same subset.

Article Snippet: Macrophages differentiated from monocyte subsets by GM-CSF from SSc-ILD patients were cultured for 7 days and subsequently co-cultured with commercially sourced human lung fibroblasts (ACBR 469, Cell Systems, Kirkland, WA, USA) for 5 days, with or without treatment with a TREM2 inhibitor (BLP-NR018, Alomone Labs, Jerusalem, Israel).

Techniques: Derivative Assay, Activation Assay, Expressing, Co-Culture Assay, Cell Culture, RNA Sequencing, Western Blot, Gene Expression, Inhibition, Control

Journal: Frontiers in Immunology

Article Title: CD14 + CD16 + monocyte-derived TREM2 macrophages promote lung fibrosis in systemic sclerosis–interstitial lung disease

doi: 10.3389/fimmu.2026.1748574

Figure Lengend Snippet: TREM2 macrophages and fibrotic progression in SSc-ILD. This schematic illustrates the proposed mechanism by which GM-CSF–induced monocyte-derived macrophages differentiate and promote lung fibrosis in patients with SSc-ILD. In SSc-ILD, recruited monocytes stimulated by GM-CSF upregulate TREM2 and GPNMB , leading to increased secretion of cytokines such as CCL2 and TGF-β1. CCL2 promotes additional recruitment of monocytes via the CCL2-CCR2 axis. These TREM2 + macrophages enhance fibroblast activation through TGF-β1 production, driving fibroblast to myofibroblast differentiation and contributing to fibrotic remodeling in the lung.

Article Snippet: Macrophages differentiated from monocyte subsets by GM-CSF from SSc-ILD patients were cultured for 7 days and subsequently co-cultured with commercially sourced human lung fibroblasts (ACBR 469, Cell Systems, Kirkland, WA, USA) for 5 days, with or without treatment with a TREM2 inhibitor (BLP-NR018, Alomone Labs, Jerusalem, Israel).

Techniques: Derivative Assay, Activation Assay

Journal: Brain, Behavior, & Immunity - Health

Article Title: Increased circulating TREM2 + microglial extracellular vesicles in aged APP/PS1 Alzheimer's disease rats

doi: 10.1016/j.bbih.2026.101261

Figure Lengend Snippet: TMEM119 + /TREM2 + EVs are increased in 15-month-old APP/PS1 rats. A) Example nanoscale flow cytometry scatter plots of TMEM119, TREM2 and dual-positive EVs. B) TMEM119 + /TREM2 + events/μl labelled in 3-, 9-, and 15-month wildtype and APP/PS1 rat plasma assessed using a 2-way ANOVA (genotype ✕ sex). C) Size distribution of TMEM119 +/ TREM2 + EVs based on standardized reference beads. D) Western blot of TMEM119 and TREM2 from, immunoprecipitated TMEM119 EVs, total rat plasma EVs, and whole cell lysate. E) Representative immunofluorescent 20 ✕ images of TMEM119 and TREM2 in 15-month-old APP/PS1 hippocampus. Scale bar indicates 10 μm ∗ Indicates statistical significance ( p < 0.05) Data represent the group mean ± SEM. n = 10-12 males and females per group. LALS, long angle light scatter; SALS, short angle light scatter.

Article Snippet: Membranes were washed for 3 × 10 min with TBST prior to incubation with anti-mouse (TMEM119, ⍺-tubulin) or anti-rabbit (TREM2) HRP-conjugated secondary antibodies (1:10,000, Jackson Laboratories) for 1 h at room temperature.

Techniques: Flow Cytometry, Clinical Proteomics, Western Blot, Immunoprecipitation

Journal: Brain, Behavior, & Immunity - Health

Article Title: Increased circulating TREM2 + microglial extracellular vesicles in aged APP/PS1 Alzheimer's disease rats

doi: 10.1016/j.bbih.2026.101261

Figure Lengend Snippet: TREM2 mRNA and protein levels differ by age and genotype in the hippocampus. A) Coronal section for the hippocampal region of interest. B) qPCR measurement of TMEM119 and TREM2 in 3-, 9-, and 15-month WT and APP/PS1 hippocampal RNA isolates assessed using 2-way ANOVAs (age ✕ genotype). C-E) Western blot of TMEM119 and TREM2 and corresponding quantification in hippocampal protein isolates from 3-, 9-, and 15-month WT and APP/PS1 rats assessed using t -tests. ∗ Indicates statistical significance ( p < 0.05). Data represent the group mean ± SEM. n = 2-3 males and 2-3 females per group.

Article Snippet: Membranes were washed for 3 × 10 min with TBST prior to incubation with anti-mouse (TMEM119, ⍺-tubulin) or anti-rabbit (TREM2) HRP-conjugated secondary antibodies (1:10,000, Jackson Laboratories) for 1 h at room temperature.

Techniques: Western Blot

Journal: Brain, Behavior, & Immunity - Health

Article Title: Increased circulating TREM2 + microglial extracellular vesicles in aged APP/PS1 Alzheimer's disease rats

doi: 10.1016/j.bbih.2026.101261

Figure Lengend Snippet: Increased TREM2 mRNA in the corpus callosum of 15-month-old rats. A) Coronal section for the corpus callosum region of interest. B) qPCR measurement of TMEM119 and TREM2 in 3-, 9-, and 15-month WT and APP/PS1 corpus callosum RNA isolates assessed using 2-way ANOVAs (age ✕ genotype). C-E) Western blot of TMEM119 and TREM2 and corresponding quantification in corpus callosum protein isolates from 3-, 9-, and 15-month WT and APP/PS1 rats assessed using t -tests. ∗ Indicates statistical significance ( p < 0.05). Data represent the group mean ± SEM. n = 2-3 males and 2-3 females per group.

Article Snippet: Membranes were washed for 3 × 10 min with TBST prior to incubation with anti-mouse (TMEM119, ⍺-tubulin) or anti-rabbit (TREM2) HRP-conjugated secondary antibodies (1:10,000, Jackson Laboratories) for 1 h at room temperature.

Techniques: Western Blot

Journal: Brain, Behavior, & Immunity - Health

Article Title: Increased circulating TREM2 + microglial extracellular vesicles in aged APP/PS1 Alzheimer's disease rats

doi: 10.1016/j.bbih.2026.101261

Figure Lengend Snippet: Increased histological TREM2 expression in aged APP/PS1 rats. A) Quantification of TREM2 cell density in the hippocampus of 3-, 9-, and 15-month WT and APP/PS1 rats assessed using t -tests. B) Representative 20 ✕ images of TREM2 + cells in the hippocampus of 15-month WT and APP/PS1 rats. C) Quantification of TREM2 cell density in the corpus callosum of 3-, 9-, and 15-month WT and APP/PS1 rats assessed using t -tests. D) Representative 20 ✕ images of TREM2 + cells in the corpus callosum of 15-month WT and APP/PS1 rats. Scale bar indicates 25 μm ∗ Indicates statistical significance ( p < 0.05). Data represent the group mean ± SEM. n = 4 males and 4 females per group.

Article Snippet: Membranes were washed for 3 × 10 min with TBST prior to incubation with anti-mouse (TMEM119, ⍺-tubulin) or anti-rabbit (TREM2) HRP-conjugated secondary antibodies (1:10,000, Jackson Laboratories) for 1 h at room temperature.

Techniques: Expressing

Journal: Brain, Behavior, & Immunity - Health

Article Title: Increased circulating TREM2 + microglial extracellular vesicles in aged APP/PS1 Alzheimer's disease rats

doi: 10.1016/j.bbih.2026.101261

Figure Lengend Snippet: Impaired spatial memory associates with increased TMEM119 + /TREM2 + EVs in 15-month-old rats. A) Simple linear regression between TMEM119 + /TREM2 + events/μl and total RAWM errors in 3-, 9-, and 15-month WT and APP/PS1 rats. n = 10-12 males and females per group.

Article Snippet: Membranes were washed for 3 × 10 min with TBST prior to incubation with anti-mouse (TMEM119, ⍺-tubulin) or anti-rabbit (TREM2) HRP-conjugated secondary antibodies (1:10,000, Jackson Laboratories) for 1 h at room temperature.

Techniques: