Fig. 4: TIM4 controls capture and cross-presentation of cell-associated antigens in lung resident cDC1. | Nature Communications

Fig. 4: TIM4 controls capture and cross-presentation of cell-associated antigens in lung resident cDC1.

From: TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses

Fig. 4

a Mice were challenged with KP-BFP and treated with blocking antibodies to TIM4 or isotype control as depicted. The uptake by lung cDC1 was quantified 5 days after tumor challenge. Dot plot and quantification of one representative of two experiment with n = 3 mice/group are shown. b Control mice or late KP tumor bearing mice were pre-treated with isotype control or αTIM4 antibodies and challenged with CTV-labeled apoptotic thymocytes. The percentage of lung phagocytes associated to fluorescence was evaluated by flow-cytometry 2 h after challenge. Representative plots and quantification of two independent experiments are shown, Isotype n = 7, Isotype KP(l) = 9, αTIM4 n = 8, αTIM4-KP(l) n = 3. c Uptake of pH rodo loaded thymocytes by lung cDC1 in WT and Timd4−/− mice. Representative histograms and quantifications (percentage and MFI of pH rodo+ cDC1) for one of three independent experiments with n = 3 mice/group are shown. d Cross-presentation by lung cDC1 (labeling with 25D1.16 antibody specific for MHC class-I:OVA peptide complex) in day 7 KP-OVA bearing animals treated with TIM4 blockade. Representative histograms showing MFI values and quantification of five animals/group in two independent experiments. e In vivo proliferation of adoptively transferred OT-I induced by i.t. injection of OVA-loaded apoptotic thymocytes, in the presence of TIM4 blocking antibodies or isotype control as depicted in the scheme. Graphs show frequencies and absolute numbers of proliferated CD8+ T cells in the MLN (at least one cycle of proliferation). Data are representative of two independent experiments. % proliferation Isotype n = 8, αTIM4 n = 7; Absolute numbers five mice/group. f Ex-vivo OT-I proliferation induced by cell-sorted cDC1 from day 7 KP-OVA lung tumors under TIM4 blockade or isotype treatment. Representative dilution profile and quantification from three independent experiments (each point corresponds to the pool cDC1 from three mice), Isotype n = 9, αTIM4 n = 7. g As in f, cDC1 were isolated from day 7 KP-OVA lung tumors induced in WT or Tim4d−/− animals (n = 5 mice in two independent experiments). All data are depicted as mean ± SEM. Significance was determined by one-way ANOVA followed by Tukey’s post-test for b, or two-tailed unpaired t-test. Source data are provided as a Source Data file.

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