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

doi:10.1084/jem.193.1.35

Published online 27 December 2000.

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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 Yoneyama^a,b, Kenjiro Matsuno^d, Yanyun Zhang^a, Masako Murai^a,b, Meiji Itakura^a, Sho Ishikawa^a, Go Hasegawa^c, Makoto Naito^c, Hitoshi Asakura^b, and Kouji Matsushima^a
^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

Correspondence to: Kouji Matsushima, Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyoku, Tokyo 113-0033, Japan. Tel:81-3-5841-3431 Fax:81-3-5684-2297 E-mail:koujim{at}m.u-tokyo.ac.jp.

We have studied the recruitment and roles of distinct dendriticcell (DC) precursors from the circulation into Propionibacteriumacnes–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 newlyformed granulomas. Recruited DCs later migrated to the portalarea to interact with T cells in what we term "portal tract–associatedlymphoid tissue" (PALT). Macrophage inflammatory protein 1 ${alpha}$ attractedblood DC precursors to the sinusoidal granuloma, whereas secondarylymphoid organ chemokine (SLC) attracted mature DCs to the newlyidentified PALT. Anti-SLC antibody diminished PALT expansionwhile exacerbating granuloma formation. Therefore, circulatingDC precursors can migrate into a solid organ like liver, andparticipate in the granulomatous reaction in response to specificchemokines.

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

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