Limits...
Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease.

Yoneyama H, Matsuno K, Zhang Y, Murai M, Itakura M, Ishikawa S, Hasegawa G, Naito M, Asakura H, Matsushima K - J. Exp. Med. (2001)

Bottom Line: 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 1alpha attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT.Therefore, circulating DC precursors can migrate into a solid organ like liver, and participate in the granulomatous reaction in response to specific chemokines.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Preventive Medicine, School of Medicine The University of Tokyo, Bunkyoku, Tokyo 113-0033, Japan.

ABSTRACT
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 1alpha 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.

Show MeSH

Related in: MedlinePlus

Formation of PALT. (a–f) Immunohistochemistry for B220 (a, red; type IV collagen, brown), FDC-M1 (b, brown), CR1 (c, brown), CD4 (d, blue; DEC205, brown; BrdU, red), PNAd (e, brown), and MOMA-1 (f, red) in PALT (day 7). Original magnifications: ×400. B, bile duct; P, portal vein; L, lymphatic. (g) Kinetics of BrdU+CD4+ cells in PALT and the sinusoidal granuloma (GR). Mean ± SD (n = 6). Asterisk, P < 0.05.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2195882&req=5

Figure 6: Formation of PALT. (a–f) Immunohistochemistry for B220 (a, red; type IV collagen, brown), FDC-M1 (b, brown), CR1 (c, brown), CD4 (d, blue; DEC205, brown; BrdU, red), PNAd (e, brown), and MOMA-1 (f, red) in PALT (day 7). Original magnifications: ×400. B, bile duct; P, portal vein; L, lymphatic. (g) Kinetics of BrdU+CD4+ cells in PALT and the sinusoidal granuloma (GR). Mean ± SD (n = 6). Asterisk, P < 0.05.

Mentions: Immunohistochemistry revealed that the P. acnes–induced portal infiltrate contained B220+ B cell aggregations (Fig. 6 a), which were rarely seen in the sinusoidal area. Follicular DC (FDC)-reactive markers 29, FDC-M1+ and CR1+ cells, were also found in these portal B cell aggregates (Fig. 6b and Fig. c) like B cell follicles, although typical germinal centers were not observed. In addition, CD4+ T cells were found between B cell follicles and bile ducts (Fig. 6 d). The pattern was distinct from CD4+ T cells in sinusoidal granulomas, which localized in the periphery of the granuloma (Fig. 1 c). The portal CD4+ T cell clusters were associated with high endothelial venule (HEV)-like vessels as revealed by PNAd 30 staining (Fig. 6 e). On the outer rim of these B and T foci, macrophages were recognized by MOMA-1 (Fig. 6 f), ER-TR9, and antisialoadhesin Ab (data not shown). Accordingly, the portal infiltrates actually resembled the organization of lymphoid tissue in peripheral LNs, which contain B cell follicles, T cell areas, and macrophages. Therefore, P. acnes administration induced “tertiary” portal lymphoid tissue as well as sinusoidal granulomas.


Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease.

Yoneyama H, Matsuno K, Zhang Y, Murai M, Itakura M, Ishikawa S, Hasegawa G, Naito M, Asakura H, Matsushima K - J. Exp. Med. (2001)

Formation of PALT. (a–f) Immunohistochemistry for B220 (a, red; type IV collagen, brown), FDC-M1 (b, brown), CR1 (c, brown), CD4 (d, blue; DEC205, brown; BrdU, red), PNAd (e, brown), and MOMA-1 (f, red) in PALT (day 7). Original magnifications: ×400. B, bile duct; P, portal vein; L, lymphatic. (g) Kinetics of BrdU+CD4+ cells in PALT and the sinusoidal granuloma (GR). Mean ± SD (n = 6). Asterisk, P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195882&req=5

Figure 6: Formation of PALT. (a–f) Immunohistochemistry for B220 (a, red; type IV collagen, brown), FDC-M1 (b, brown), CR1 (c, brown), CD4 (d, blue; DEC205, brown; BrdU, red), PNAd (e, brown), and MOMA-1 (f, red) in PALT (day 7). Original magnifications: ×400. B, bile duct; P, portal vein; L, lymphatic. (g) Kinetics of BrdU+CD4+ cells in PALT and the sinusoidal granuloma (GR). Mean ± SD (n = 6). Asterisk, P < 0.05.
Mentions: Immunohistochemistry revealed that the P. acnes–induced portal infiltrate contained B220+ B cell aggregations (Fig. 6 a), which were rarely seen in the sinusoidal area. Follicular DC (FDC)-reactive markers 29, FDC-M1+ and CR1+ cells, were also found in these portal B cell aggregates (Fig. 6b and Fig. c) like B cell follicles, although typical germinal centers were not observed. In addition, CD4+ T cells were found between B cell follicles and bile ducts (Fig. 6 d). The pattern was distinct from CD4+ T cells in sinusoidal granulomas, which localized in the periphery of the granuloma (Fig. 1 c). The portal CD4+ T cell clusters were associated with high endothelial venule (HEV)-like vessels as revealed by PNAd 30 staining (Fig. 6 e). On the outer rim of these B and T foci, macrophages were recognized by MOMA-1 (Fig. 6 f), ER-TR9, and antisialoadhesin Ab (data not shown). Accordingly, the portal infiltrates actually resembled the organization of lymphoid tissue in peripheral LNs, which contain B cell follicles, T cell areas, and macrophages. Therefore, P. acnes administration induced “tertiary” portal lymphoid tissue as well as sinusoidal granulomas.

Bottom Line: 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 1alpha attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT.Therefore, circulating DC precursors can migrate into a solid organ like liver, and participate in the granulomatous reaction in response to specific chemokines.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Preventive Medicine, School of Medicine The University of Tokyo, Bunkyoku, Tokyo 113-0033, Japan.

ABSTRACT
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 1alpha 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.

Show MeSH
Related in: MedlinePlus