The Journal of Experimental Medicine
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Published online 1 January 2001.
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© The Rockefeller University Press, 0022-1007/2001/1/35/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 1, January 1, 2001 35-50

Original Article

Regulation by Chemokines of Circulating Dendritic Cell Precursors, and the Formation of Portal Tract–Associated Lymphoid Tissue, in a Granulomatous Liver Disease

Hiroyuki Yoneyamaa,b, Kenjiro Matsunod, Yanyun Zhanga, Masako Muraia,b, Meiji Itakuraa, Sho Ishikawaa, Go Hasegawac, Makoto Naitoc, Hitoshi Asakurab, and Kouji Matsushimaa

a Department of Molecular Preventive Medicine, School of Medicine and Core Research for Evolutional Science and Technology (CREST), The University of Tokyo, Bunkyoku, Tokyo 113-0033, Japan
b Third Department of Internal Medicine, Niigata University School of Medicine, Niigata-shi, Niigata 951-8122, Japan
c Second Department of Pathology, Niigata University School of Medicine, Niigata-shi, Niigata 951-8122, Japan
d Department of Anatomy II, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan
Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyoku, Tokyo 113-0033, Japan.81-3-5684-229781-3-5841-3431

koujim{at}m.u-tokyo.ac.jp

We have studied the recruitment and roles of distinct dendritic cell (DC) precursors from the circulation into Propionibacterium acnes–induced granulomas in mouse liver. During infection, F4/80–B220–CD11c+ DC precursors appeared in the circulation, migrated into the perisinusoidal space, and matured within newly formed granulomas. Recruited DCs later migrated to the portal area to interact with T cells in what we term "portal tract–associated lymphoid tissue" (PALT). Macrophage inflammatory protein 1{alpha} attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT. Anti-SLC antibody diminished PALT expansion while exacerbating granuloma formation. Therefore, circulating DC precursors can migrate into a solid organ like liver, and participate in the granulomatous reaction in response to specific chemokines.

Key Words: dendritic cells • CC chemokine • migration • portal system • inflammation

Abbreviations used in this paper: ALT, alanine transferase; BrdU, 5-bromo-2'-deoxyuridine; CCR, CC chemokine receptor; DC, dendritic cell; FDC, follicular DC; HEV, high endothelial venule; LD, low density; MIP, macrophage inflammatory protein; MLR, mixed leukocyte reaction; NPC, nonparenchymal cell; pAb, polyclonal Ab; PALT, portal tract–associated lymphoid tissue; PNAd, peripheral node addressin; SLC, secondary lymphoid organ chemokine.

© 2001 The Rockefeller University Press


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