Characterization of the liver-draining lymph nodes in mice and their role in mounting regional immunity to HBV

Zheng, Meijuan; Yu, Jiali; Tian, Zhigang

doi:10.1038/cmi.2012.59

Cited by 31 publications

(27 citation statements)

References 24 publications

(22 reference statements)

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“…Previous reports have identified LLNs, which are lymphoid tissues that drain the liver. (90,91) Of interest, liver-derived DC migration to LLNs can profoundly elicit T-cell activation, whereas liver-derived DC migration to MLNs minimally affects T-cell activation. (91) Therefore, LLN cells were isolated from EF and MPF mice for flow cytometric analysis (Fig.…”

Section: Sfb Monoassociation Enhances Osteoclast Differentiation and mentioning

confidence: 99%

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

et al. 2020

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The commensal gut microbiota critically regulates immunomodulatory processes that influence normal skeletal growth and maturation. However, the influence of specific microbes on commensal gut microbiota osteoimmunoregulatory actions is unknown. We have shown previously that the commensal gut microbiota enhances TH17/IL17A immune response effects in marrow and liver that have procatabolic/antianabolic actions in the skeleton. Segmented filamentous bacteria (SFB), a specific commensal gut bacterium within phylum Firmicutes, potently induces TH17/IL17A‐mediated immunity. The study purpose was to delineate the influence of SFB on commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal development. Two murine models were utilized: SFB‐monoassociated mice versus germ‐free (GF) mice and specific‐pathogen‐free (SPF) mice +/− SFB. SFB colonization was validated by 16S rDNA analysis, and SFB‐induced TH17/IL17A immunity was confirmed by upregulation of Il17a in ileum and IL17A in serum. SFB‐colonized mice had an osteopenic trabecular bone phenotype, which was attributed to SFB actions suppressing osteoblastogenesis and enhancing osteoclastogenesis. Intriguingly, SFB‐colonized mice had increased expression of proinflammatory chemokines and acute‐phase reactants in the liver. Lipocalin‐2 (LCN2), an acute‐phase reactant and antimicrobial peptide, was substantially elevated in the liver and serum of SFB‐colonized mice, which supports the notion that SFB regulation of commensal gut microbiota osteoimmunomodulatory actions are mediated in part through a gut–liver–bone axis. Proinflammatory TH17 and TH1 cells were increased in liver‐draining lymph nodes of SFB‐colonized mice, which further substantiates that SFB osteoimmune‐response effects may be mediated through the liver. SFB‐induction of Il17a in the gut and Lcn2 in the liver resulted in increased circulating levels of IL17A and LCN2. Recognizing that IL17A and LCN2 support osteoclastogenesis/suppress osteoblastogenesis, SFB actions impairing postpubertal skeletal development appear to be mediated through immunomodulatory effects in both the gut and liver. This research reveals that specific microbes critically impact commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal growth and maturation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Section: Sfb Monoassociation Enhances Osteoclast Differentiation and mentioning

confidence: 99%

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

et al. 2020

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“…The anatomic location of the liver lymph nodes has been previously described. 35 Cells were treated with red blood cell lysis buffer and then washed in Hanks' balanced salt solution. Isolation of liver granuloma cells was performed as previously described.…”

Section: Cell Isolation and Flow Cytometrymentioning

confidence: 99%

Lymphangiogenesis Is Induced by Mycobacterial Granulomas via Vascular Endothelial Growth Factor Receptor-3 and Supports Systemic T-Cell Responses against Mycobacterial Antigen

Harding

Ritter

Rayasam

et al. 2015

The American Journal of Pathology

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Granulomatous inflammation is characteristic of many autoimmune and infectious diseases. The lymphatic drainage of these inflammatory sites remains poorly understood, despite an expanding understanding of lymphatic role in inflammation and disease. Here, we show that the lymph vessel growth factor Vegf-c is up-regulated in Bacillus Calmette-Guerin- and Mycobacterium tuberculosis-induced granulomas, and that infection results in lymph vessel sprouting and increased lymphatic area in granulomatous tissue. The observed lymphangiogenesis during infection was reduced by inhibition of vascular endothelial growth factor receptor 3. By using a model of chronic granulomatous infection, we also show that lymphatic remodeling of tissue persists despite resolution of acute infection and a 10- to 100-fold reduction in the number of bacteria and tissue-infiltrating leukocytes. Inhibition of vascular endothelial growth factor receptor 3 decreased the growth of new vessels, but also reduced the proliferation of antigen-specific T cells. Together, our data show that granuloma-up-regulated factors increase granuloma access to secondary lymph organs by lymphangiogenesis, and that this process facilitates the generation of systemic T-cell responses to granuloma-contained antigens.

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“…However, this accelerated CFSE dilution profile and OT-I T cell accumulation was not evident in the liver-draining lymph nodes of the wild-type and Batf3 −/− recipients (Fig. 3E) (34, 35). Activated (responding) OT-I T cells isolated from the livers of wild-type and Batf3 −/− mice at 3 dpi display comparable levels and frequencies of the activation markers CD69 and CD25 (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 96%

Liver-Resident CD103+ Dendritic Cells Prime Antiviral CD8+ T Cells In Situ

Krueger

Kim

Sung

et al. 2015

The Journal of Immunology

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The liver maintains a tolerogenic environment to avoid unwarranted activation of its resident immune cells upon continuous exposure to food and bacterially derived antigens. However, in response to hepatotropic viral infection, the liver’s ability to switch from a hyporesponsive to a pro-inflammatory environment is mediated by select sentinels within the parenchyma. To determine the contribution of hepatic DCs to activate naïve CD8+ T cells, we first characterized resident DC subsets in the murine liver. Liver DCs exhibit unique properties, including the expression of CD8α (traditionally lymphoid tissue specific), CD11b and CD103 markers. In both steady-state and following viral infection, liver CD103+ DCs express high levels of MHC-II, CD80 and CD86, and contribute to the high number of activated CD8+ T cells. Importantly, viral infection in the Batf3−/− mouse, which lacks CD8α+ and CD103+ DCs in the liver, exhibits a three-fold reduction in the proliferative response of antigen-specific CD8+ T cells. Limiting DC migration out of the liver does not significantly alter CD8+ T cell responsiveness, indicating that CD103+ DCs initiate the induction of CD8+ T cell responses in situ. Collectively, these data suggest that liver resident CD103+ DCs are highly immunogenic in response to hepatotropic viral infection and serve as a major APC to support the local CD8+ T cell response. It also implies that CD103+ DCs present a promising cellular target for vaccination strategies to resolve chronic liver infections.

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Characterization of the liver-draining lymph nodes in mice and their role in mounting regional immunity to HBV

Cited by 31 publications

References 24 publications

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

Lymphangiogenesis Is Induced by Mycobacterial Granulomas via Vascular Endothelial Growth Factor Receptor-3 and Supports Systemic T-Cell Responses against Mycobacterial Antigen

Liver-Resident CD103+ Dendritic Cells Prime Antiviral CD8+ T Cells In Situ

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