Fig 2: Body adipose overdevelopment, bone mass loss, and gut atrophy in HFD-induced murine obesity. Increased body weight, blood glucose levels (a) as well as visceral fat and subcutaneous fat development in obese mice (b); scale bar, 1.5 cm. Decreased colon length and villi loss (c and e); scale bar of upper panels, 200 μm; scale bar of lower panels, 100 µm. Losses of PAS-stained mucin, CLDN-1, and TJP1 levels, but increased IL-17 levels in colon goblet cells of obese mice (d and e); scale bar, 15 μm. Sparse trabecular bone network (f); scale bar, 50 μm and decreased trabecular BMD, Tb.Th, BV/TV, Tb.N and increased Tb.Sp and SMI in obese mice (g). Decreased fluorescence calcein-labelling, MAR, and BFR/BS upon HFD consumption (h); scale bar, 20 μm. Mice were fed HFD or CD for 6 months. Data are means ± standard errors calculated from 6 mice. Asterisks (*) stand for significant difference (P < 0.05) analyzed by Kolmogorov–Smirnov test and Student t-test

Fig 3: Proposed pathway by which increased IL-17 levels and activation of the IL-17 receptor in microglia induces neuroinflammation and activation of the TNFα-TNFR1-S1PR2-CCL2-BDNF-TrkB pathway in cerebellum of hyperammonemic rats. IL-17 levels and membrane expression and activation of the IL-17 receptor are enhanced mainly in microglia of hyperammonemic rats, leading to increased activation of STAT3 and NF-κB, which increase the formation of IL-17 and TNFα, respectively. TNFα released by microglia activates its receptor TNFR1 in Purkinje neurons, leading to activation of the TNFα-TNFR1-S1PR2-CCL2 pathway in Purkinje neurons. CCL2 released from Purkinje neurons activates CCR2 in microglia, inducing microglia activation and increased content of BDNF. BDNF released from microglia activates TrkB-mediated signals in neurons, leading to increased membrane expression of KCC2. This would enhance GABAergic neurotransmission and induce motor incoordination. The effects of hyperammonemia are indicated by red arrows (↑). Blockade with anti-IL-17 antibody is shown in green

Fig 4: Effects of BAC on the infiltration of CD4+ T cells in the conjunctiva and CLNs. (A) Representative image of CD4+ T cell staining in the conjunctiva. Scale bars: 50 µm. (B) Statistical analysis of the number of CD4+ T cells in the conjunctiva. The data are shown as the mean ± SD. **P < 0.01 (n = 5). (C) Representative FCM plots of CD4+CD69+ T cells. (D) Representative image of IFN-γ+CD4+ and IL-17+CD4+ T cells in the conjunctiva. Scale bars: 50 µm. (E) Representative FCM plots of IFN-γ+CD4+ and IL-17+CD4+ T cells.

Fig 5: γδT17 cells were elevated in H. felis-infected mice. (A) Interleukin-17 (IL-17) levels in the gastric homogenates at 8 months postinfection. (B) IL-17 messenger RNA (mRNA) level in the stomach at 8 months postinfection. (C) Representative immunohistochemistry (IHC) image showing in situ IL-17 in the stomach of H. felis-infected and control mice and (D) corresponding histoscores. Original magnification, 400×. (E) Percentage of CD4+, CD8+, and γδT cells among CD45+ cells in the spleen of H. felis-infected mice and control mice at 8 months postinfection. (F) Percentage of CD4+IL-17+(Th17), CD8+IL-17+(Tc17), and TCRγδ+IL-17+(γδT17) cells in the spleen from H. felis-infected and control mice at 8 months (left), and representative flow cytometric plots of the same gated with IL-17+CD3+ T cells (right). (G) The percentage of Th17, Tc17, and γδT17 cells among CD45+ cells in the spleen at 8, 11, and 14 months postinfection. (H) Time-dependent increase in γδT17 cells with the progression of chronic H. felis infection; 8 months (control, n = 4; H. felis, n = 4), 11 months (control, n = 5; H. felis, n = 4), and 14 months (control, n = 5; H. felis, n = 10). *P < 0.05, **P < 0.01.