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. 2024 Feb 13;11(16):2306066. doi: 10.1002/advs.202306066

Figure 6.

Figure 6

The characteristic AILI microenvironment visualized by DAOSLIMIT in living mice correlates well with human DILI progression. A‐B) Timelapse data captured by DAOSLIMIT showing the interactions between monocytes and CD63+ ECs in LysM cre Mas1 f/f‐APAP mouse (A) and LysM cre Rosa26(R26)‐tdTomato‐APAP mouse (B). The curves of cell distances are shown on the right. Scale bar: 50 µm. C) mIHC of CD31+MYC+ ECs, CD68+CD14−MMP12+ Mψ and CD14+ monocytes in the livers of healthy individuals and patients with DILI (n = 14 healthy and 47 with DILI). Scale bar: 50 µm and 20 µm. D) Spatial localization of CD31+MYC+ ECs, CD68+CD14−MMP12+ Mψ and CD14+ monocytes within injured region (n = 14 healthy and 47 with DILI). Scale bar: 200 µm. E) mIHC of CD31+MYC+ ECs, CD68+CD14−MMP12+ Mψ and CD14+ monocytes in the livers of patients with chronic hepatitis B (CHB), alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), Non‐AILI and AILI (n = 10 with CHB, 5 with ALD, 5 with NAFLD, 5 with AIH, 5 with PBC, 32 with Non‐AILI and 15 with AILI). Scale bar: 100 µm and 20 µm. F) Quantification of CD31+MYC+ ECs, CD68+CD14−MMP12+ Mψ and CD14+ monocytes for mIHC as shown in E (n = 10 with CHB, 5 with ALD, 5 with NAFLD, 5 with AIH, 5 with PBC, 32 with Non‐AILI and 15 with AILI; two‐sided Student's t‐test and two‐sided Mann‐Whitney U test; p = 5.00 × 10−6, 5.30 × 10−4, 5.30 × 10−4, 6.24 × 10−4, 6.24 × 10−4, 1.00 × 10−5, 5.00 × 10−6, 8.00 × 10−6, 1.20 × 10−5, 1.30 × 10−5, 5.84 × 10−1 from left to right for quantification of CD31+MYC+ ECs; p = 9.00 × 10−6, 1.01 × 10−3, 1.01 × 10−3, 8.62 × 10−4, 1.18 × 10−3, 8.20 × 10−5, 2.80 × 10−5, 1.70 × 10−5, 1.00 × 10−5, 3.70 × 10−5, 9.13 × 10−2 from left to right for quantification of CD68+CD14−MMP12+ Mψ; p = 6.79 × 10−1, 8.24 × 10−1, 6.72 × 10−3, 4.77 × 10−1, 1.10 × 10−1, 2.22 × 10−1, 1.90 × 10−1, 5.20 × 10−3, 8.87 × 10−2, 4.46 × 10−2, 2.18 × 10−1 from left to right for quantification of CD14+ monocytes). G) Correlation analysis between CD31+MYC+ ECs, CD68+CD14−MMP12+ Mψ, CD14+ monocytes and DILI pathology parameters (n =  47 patients; Pearson correlation; color and circle size indicate correlation). In all graphs data are presented as mean ± SD, *p < 0.05; **p < 0.01; ***p < 0.001; NS, non‐significant.