Skip to main content

Advertisement

SpringerLink
Log in

Recruitment of dendritic cells to pathological niches in inflamed liver

  • SPECIAL REVIEW SERIES: New ultrastructural discoveries in the pathophysiology of liver diseases
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

The liver is a specialized organ for host defense and immunity. Recruitment of dendritic cells (DCs) is crucial to host defense in a granulomatous liver disease in mice. In response to danger signals, DC precursors are mobilized de novo into the circulation. Myeloid DC (mDC) precursors are recruited to perisinusoidal spaces and activated to form granulomas. Recruited mDCs subsequently extravasate into Disse’s space and migrate to the portal area to induce portal tract-associated lymphoid tissue (PALT). Some mDCs are remobilized into draining hepatic lymph nodes (LNs) to prime antigen-specific CD4+ helper T cells. Kupffer cell-derived CCL3/MIP-1α attracts mDC precursors to the sinusoidal granulomas, whereas PALT composed cell-derived CCL21/SLC attracts activated mDCs to the T-cell zone of PALT. Inflammatory cytokines modulate this sinusoid-portal migration through IL-1R/TLR signaling. Recruited mDCs themselves also produce several chemokines and cytokines that modulate T-cell responses. A unique trafficking of circulating mDC precursors within the inflammation-associated, newly formed compartments (“pathological niches”) is strictly regulated by both homeostatic and inducible chemokines and determines the final efficiency of the immunity in this organ.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. J Banchereau RM Steinman (1998) ArticleTitleDendritic cells and the control of immunity Nature (Lond) 392 245–252 Occurrence Handle10.1038/32588

    Article  Google Scholar 

  2. FR Carbone WR Heath (2003) ArticleTitleThe role of dendritic cell subsets in immunity to viruses Curr Opin Immunol 15 416–420 Occurrence Handle10.1016/S0952-7915(03)00074-8 Occurrence Handle12900273

    Article  PubMed  Google Scholar 

  3. K Shortman YJ Liu (2002) ArticleTitleMouse and human dendritic cell subtypes Nat Rev Immunol 2 151–161 Occurrence Handle11913066

    PubMed  Google Scholar 

  4. K Matsuno T Ezaki (2000) ArticleTitleDendritic cell dynamics in the liver and hepatic lymph Int Rev Cytol 197 83–136 Occurrence Handlefull_text||10.1016/S0074-7696(00)97003-7 Occurrence Handle10761116

    Article  PubMed  Google Scholar 

  5. S Kudo K Matsuno T Ezaki M Ogawa (1997) ArticleTitleA novel migration pathway for rat dendritic cells from the blood: hepatic sinusoids-lymph translocation J Exp Med 185 777–784 Occurrence Handle10.1084/jem.185.4.777 Occurrence Handle9034155

    Article  PubMed  Google Scholar 

  6. K Matsuno T Ezaki S Kudo Y Uehara (1996) ArticleTitleA life stage of particle-laden rat dendritic cells in vivo: their terminal division, active phagocytosis, and translocation from the liver to the draining lymph J Exp Med 183 1865–1878 Occurrence Handle10.1084/jem.183.4.1865 Occurrence Handle8666943

    Article  PubMed  Google Scholar 

  7. M Naito G hasegawa Y Ebe T Yamamoto (2004) ArticleTitleDifferentiation and function of kupffer cells Med Electron Microsc 37 16–28 Occurrence Handle10.1007/s00795-003-0228-x Occurrence Handle15057601

    Article  PubMed  Google Scholar 

  8. K Enomoto Y Nishikawa Y Omori T Tokairin M Yoshida N Ohi T Nishimura Y Yamamoto Q Li (2004) ArticleTitleCell biology and pathology of liver sinusoidal endothelial cells Med Electron Microsc 37 208–215 Occurrence Handle10.1007/s00795-004-0261-4 Occurrence Handle15614445

    Article  PubMed  Google Scholar 

  9. K Nakatani K Kamada S Seki Y Nakajima (2004) ArticleTitlePit cells as liver-associated natural killer cells: morphology and function Med Electron Microsc 37 29–36 Occurrence Handle10.1007/s00795-003-0229-9 Occurrence Handle15057602

    Article  PubMed  Google Scholar 

  10. H Senoo (2004) ArticleTitleStructure and function of hepatic stellate cells Med Electron Microsc 37 3–15 Occurrence Handle10.1007/s00795-003-0230-3 Occurrence Handle15057600

    Article  PubMed  Google Scholar 

  11. H David P Reinke (1987) ArticleTitleThe concept of the “perisinusoidal functional unit” of the liver – importance to pathological processes Exp Pathol 32 193–224 Occurrence Handle3327704

    PubMed  Google Scholar 

  12. T Sato H Yamamoto C Sasaki K Wake (1998) ArticleTitleMaturation of rat dendritic cells during intrahepatic translocation evaluated using monoclonal antibodies and electron microscopy Cell Tissue Res 294 503–514 Occurrence Handle10.1007/s004410051201 Occurrence Handle9799467

    Article  PubMed  Google Scholar 

  13. N Tsuji N Kawada K Ikeda H Kinoshita K Kaneda (1997) ArticleTitleImmunohistochemical and ultrastructural analyses of in situ activation of hepatic stellate cells around Propionibacterium acnes-induced granulomas in the rat liver J Submicrosc Cytol Pathol 29 125–133 Occurrence Handle9066151

    PubMed  Google Scholar 

  14. H Yoneyama K Matsuno Y Zhang M Murai M Itakura S Ishikawa G Hasegawa M Naito H Asakura K Matsushima (2001) ArticleTitleRegulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease J Exp Med 193 35–49 Occurrence Handle10.1084/jem.193.1.35 Occurrence Handle11136819

    Article  PubMed  Google Scholar 

  15. H Yoneyama K Matsuno Y Zhang T Nishiwaki M Kitabatake S Ueha S Narumi S Morikawa T Ezaki B Lu et al. (2004) ArticleTitleEvidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules Int Immunol 16 915–928 Occurrence Handle10.1093/intimm/dxh093 Occurrence Handle15159375

    Article  PubMed  Google Scholar 

  16. K Matsuno H Nomiyama H Yoneyama R Uwatoku (2002) ArticleTitleKupffer cell-mediated recruitment of dendritic cells to the liver crucial for a host defense Dev Immunol 9 143–149 Occurrence Handle10.1080/1044667031000137610 Occurrence Handle12885155

    Article  PubMed  Google Scholar 

  17. H Yoneyama A Harada T Imai M Baba O Yoshie Y Zhang H Higashi M Murai H Asakura K Matsushima (1998) ArticleTitlePivotal role of TARC, a CC chemokine, in bacteria-induced fulminant hepatic failure in mice J Clin Invest 102 1933–1941 Occurrence Handle9835618

    PubMed  Google Scholar 

  18. K Jinnouchi Y Terasaki S Fujiyama K Tomita WA Kuziel N Maeda K Takahashi M Takeya (2003) ArticleTitleImpaired hepatic granuloma formation in mice deficient in C-C chemokine receptor 2 J Pathol 200 406–416 Occurrence Handle10.1002/path.1362 Occurrence Handle12845637

    Article  PubMed  Google Scholar 

  19. A MartIn-Fontecha S Sebastiani UE Hopken M Uguccioni M Lipp A Lanzavecchia F Sallusto (2003) ArticleTitleRegulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming J Exp Med 198 615–621 Occurrence Handle10.1084/jem.20030448 Occurrence Handle12925677

    Article  PubMed  Google Scholar 

  20. AJ Grant S Goddard J Ahmed-Choudhury G Reynolds DG Jackson M Briskin L Wu SG Hubscher DH Adams (2002) ArticleTitleHepatic expression of secondary lymphoid chemokine (CCL21) promotes the development of portal-associated lymphoid tissue in chronic inflammatory liver disease Am J Pathol 160 1445–1455 Occurrence Handle11943728

    PubMed  Google Scholar 

  21. M Ogata Y Zhang Y Wang M Itakura YY Zhang A Harada S Hashimoto K Matsushima (1999) ArticleTitleChemotactic response toward chemokines and its regulation by transforming growth factor-beta-1 of murine bone marrow hematopoietic progenitor cell-derived different subset of dendritic cells Blood 93 3225–3232 Occurrence Handle10233873

    PubMed  Google Scholar 

  22. T Heath S Lowden (1998) ArticleTitlePathways of interstitial fluid and lymph flow in the liver acinus of the sheep and mouse J Anat 192 IssueIDPt 3 351–358 Occurrence Handle10.1046/j.1469-7580.1998.19230351.x Occurrence Handle9688501

    Article  PubMed  Google Scholar 

  23. H Iizasa H Yoneyama N Mukaida Y Katakoka M Naito N Yoshida E Nakashima K Matsushima (2005) ArticleTitleExacerbation of granuloma formation in IL-1 receptor antagonist-deficient mice with impaired dendritic cell maturation associated with Th2 cytokine production J Immunol 174 3273–3280 Occurrence Handle15749858

    PubMed  Google Scholar 

  24. N Fujioka N Mukaida A Harada M Akiyama T Kasahara K Kuno A Ooi M Mai K Matsushima (1995) ArticleTitlePreparation of specific antibodies against murine IL-1ra and the establishment of IL-1ra as an endogenous regulator of bacteria-induced fulminant hepatitis in mice J Leukoc Biol 58 90–98 Occurrence Handle7616110

    PubMed  Google Scholar 

  25. H Yoneyama S Narumi Y Zhang M Murai M Baggiolini A Lanzavecchia T Ichida H Asakura K Matsushima (2002) ArticleTitlePivotal role of dendritic cell-derived CXCL10 in the retention of T helper cell 1 lymphocytes in secondary lymph nodes J Exp Med 195 1257–1266 Occurrence Handle10.1084/jem.20011983 Occurrence Handle12021306

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Hiroyuki Yoneyama

  2. Department of Gastroenterology, Juntendo University School of Medicine, Shizuoka Hospital, Shizuoka, Japan

    Takafumi Ichida

Authors
  1. Hiroyuki Yoneyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takafumi Ichida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroyuki Yoneyama.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoneyama, H., Ichida, T. Recruitment of dendritic cells to pathological niches in inflamed liver. Med Mol Morphol 38, 136–141 (2005). https://doi.org/10.1007/s00795-005-0289-0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-005-0289-0

Key words

Search

Navigation