Figure 3.
Oral dysbiosis before allo-HCT worsens cGVHD. (A) The experimental procedure for HCT of OLP or control mice is shown. Recipient mice received oral ligatures 14 days before HCT. Spleen T cells and T cell–depleted bone marrow cells from donor mice were injected into irradiated recipients (control and OLP mice, n = 5 per group). Ligatures were kept during the HCT period. Mice were euthanized at day 21 after HCT for analysis. (B-C) The clinical aGVHD score and OS of BALB/c recipients of C57BL/6 donors are shown. The clinical aGVHD score was analyzed using a Wilcoxon matched-pairs signed-rank test, and the data represent the mean ± standard error (SE; control allogeneic mice vs OLP allogeneic mice, n = 5 per group). OS data were analyzed by the log-rank test (control allogeneic mice vs OLP allogeneic mice, n = 5 per group). (D) Representative images of systemic symptoms (ruffled fur and hunched posture), skin damage, and diarrhea of BALB/c recipient mice with or without ligatures at day 21 after HCT using either syngeneic (BALB/c) or allogeneic (B10.D2) donors. The OLP allogeneic recipient mice developed more severe signs of cGVHD than control mice, such as hunch (orange arrow), skin injury, blepharitis, and keratinization (orange arrowheads), and diarrhea (orange cross). (E-F) Representative cGVHD skin score and OS for BALB/c recipients of B10.D2 donor grafts are shown. The cGVHD skin score was analyzed using a Wilcoxon matched-pairs signed-rank test. Data represent the mean ± SE (control allogeneic mice vs OLP allogeneic mice, n = 5 per group). OS data were combined from 6 independent experiments and were analyzed by log-rank test (control allogeneic mice vs OLP allogeneic mice, n = 30 per allogeneic group, n = 18 per syngeneic group). (G-H) Representative cGVHD skin scores and OS of B6D2F1 recipients transplanted with C57BL/6 grafts are depicted. Chronic GVHD skin scores were analyzed using the Wilcoxon matched-pairs signed-rank test and are depicted as means ± SE (control allogeneic mice vs OLP allogeneic mice, n = 5 per group). OS data shown are combined from 4 independent experiments and were analyzed using the log-rank test (control allogeneic mice vs OLP allogeneic mice, n = 20 per allogeneic group, n = 12 per syngeneic group). (I-J) Representative cGVHD skin scores and OS of B6D2F1 recipients transplanted with C57BL/6 grafts using PTCy are depicted. Chronic GVHD skin scores were analyzed using a Wilcoxon matched-pairs signed-rank test with the data shown as means ± SE (n = 5 per group). OS data were analyzed by the log-rank test (n = 5 per group). (K) Representative images of the skin, liver, small intestine, large intestine, and salivary gland stained by hematoxylin and eosin of BALB/c recipients transplanted with B10.D2 grafts at day 21 after HCT. Scale bar, 100 μm. (L) Pathological cGVHD scores of the skin, liver, small intestine, large intestine, and salivary gland at day 21 after HCT. Pathological scores were analyzed by the Mann-Whitney U test and are represented as means ± SD (control allogeneic mice vs OLP allogeneic mice, n = 4-6 per allogeneic group, n = 3 per syngeneic group, ∗P < .05; and ∗∗P < .01). Panels B through E, G, and I through L are representative data of 3 independent experiments. Syn, syngeneic.

Oral dysbiosis before allo-HCT worsens cGVHD. (A) The experimental procedure for HCT of OLP or control mice is shown. Recipient mice received oral ligatures 14 days before HCT. Spleen T cells and T cell–depleted bone marrow cells from donor mice were injected into irradiated recipients (control and OLP mice, n = 5 per group). Ligatures were kept during the HCT period. Mice were euthanized at day 21 after HCT for analysis. (B-C) The clinical aGVHD score and OS of BALB/c recipients of C57BL/6 donors are shown. The clinical aGVHD score was analyzed using a Wilcoxon matched-pairs signed-rank test, and the data represent the mean ± standard error (SE; control allogeneic mice vs OLP allogeneic mice, n = 5 per group). OS data were analyzed by the log-rank test (control allogeneic mice vs OLP allogeneic mice, n = 5 per group). (D) Representative images of systemic symptoms (ruffled fur and hunched posture), skin damage, and diarrhea of BALB/c recipient mice with or without ligatures at day 21 after HCT using either syngeneic (BALB/c) or allogeneic (B10.D2) donors. The OLP allogeneic recipient mice developed more severe signs of cGVHD than control mice, such as hunch (orange arrow), skin injury, blepharitis, and keratinization (orange arrowheads), and diarrhea (orange cross). (E-F) Representative cGVHD skin score and OS for BALB/c recipients of B10.D2 donor grafts are shown. The cGVHD skin score was analyzed using a Wilcoxon matched-pairs signed-rank test. Data represent the mean ± SE (control allogeneic mice vs OLP allogeneic mice, n = 5 per group). OS data were combined from 6 independent experiments and were analyzed by log-rank test (control allogeneic mice vs OLP allogeneic mice, n = 30 per allogeneic group, n = 18 per syngeneic group). (G-H) Representative cGVHD skin scores and OS of B6D2F1 recipients transplanted with C57BL/6 grafts are depicted. Chronic GVHD skin scores were analyzed using the Wilcoxon matched-pairs signed-rank test and are depicted as means ± SE (control allogeneic mice vs OLP allogeneic mice, n = 5 per group). OS data shown are combined from 4 independent experiments and were analyzed using the log-rank test (control allogeneic mice vs OLP allogeneic mice, n = 20 per allogeneic group, n = 12 per syngeneic group). (I-J) Representative cGVHD skin scores and OS of B6D2F1 recipients transplanted with C57BL/6 grafts using PTCy are depicted. Chronic GVHD skin scores were analyzed using a Wilcoxon matched-pairs signed-rank test with the data shown as means ± SE (n = 5 per group). OS data were analyzed by the log-rank test (n = 5 per group). (K) Representative images of the skin, liver, small intestine, large intestine, and salivary gland stained by hematoxylin and eosin of BALB/c recipients transplanted with B10.D2 grafts at day 21 after HCT. Scale bar, 100 μm. (L) Pathological cGVHD scores of the skin, liver, small intestine, large intestine, and salivary gland at day 21 after HCT. Pathological scores were analyzed by the Mann-Whitney U test and are represented as means ± SD (control allogeneic mice vs OLP allogeneic mice, n = 4-6 per allogeneic group, n = 3 per syngeneic group, ∗P < .05; and ∗∗P < .01). Panels B through E, G, and I through L are representative data of 3 independent experiments. Syn, syngeneic.

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