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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: 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).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.

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Identification of DCs in hepatic granulomas. (a) Phenotype of granuloma-derived NPCs and LD cells on day 7. (b) Primary allogeneic MLR of granuloma-derived liver LD cells, normal liver LD cells, spleen LD cells, and responder cells alone. Three mice per group and 1,000 total cells/smear were examined. Representative data from six experiments. Mean ± SD (n = 3).
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Figure 2: Identification of DCs in hepatic granulomas. (a) Phenotype of granuloma-derived NPCs and LD cells on day 7. (b) Primary allogeneic MLR of granuloma-derived liver LD cells, normal liver LD cells, spleen LD cells, and responder cells alone. Three mice per group and 1,000 total cells/smear were examined. Representative data from six experiments. Mean ± SD (n = 3).

Mentions: Mice exposed to P. acnes by day 7 developed numerous granulomas in the liver (20; Fig. 1, a–g). F4/80+ cells including Kupffer cells and inflammatory macrophages 28 were evenly distributed throughout the granulomas (Fig. 1 f), whereas CD4+ cells localized in the periphery (Fig. 1 c). In addition, cells with the markers of DCs 11926, such as CD11c, DEC-205, M342, MHC class II, and CD86, were also distributed within granulomas (Fig. 1, a–e). We then investigated LD cells recovered on Nycodenz gradients from the NPC fraction of a granulomatous liver. A majority of LD cells actually had features of DCs, such as an eccentric irregular nucleus and a cytoplasmic membrane with ruffled projections (data not shown). The cells were MHC class IIhigh, CD11c+, DEC-205+, ICAM-1+, CD3ε−, B220−, CD8α−, Gr-1−, and expressed moderate levels of CD86, LFA-1, and CD11b (Fig. 2 a). In a functional study, they induced considerable proliferation of allogeneic T cells in vitro, compared with normal liver- and spleen-derived LD cells (Fig. 2 b), demonstrating that the granuloma contained functionally mature DCs. Moreover, DEC-205+ cells were in close contact with CD4+ T cells, many of which were in a proliferative stage, as evidenced by in situ BrdU labeling (Fig. 1 c). This suggests that DCs in the granuloma have potent antigen-presenting function and can activate T cells in situ.


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)

Identification of DCs in hepatic granulomas. (a) Phenotype of granuloma-derived NPCs and LD cells on day 7. (b) Primary allogeneic MLR of granuloma-derived liver LD cells, normal liver LD cells, spleen LD cells, and responder cells alone. Three mice per group and 1,000 total cells/smear were examined. Representative data from six experiments. Mean ± SD (n = 3).
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Related In: Results  -  Collection

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

Figure 2: Identification of DCs in hepatic granulomas. (a) Phenotype of granuloma-derived NPCs and LD cells on day 7. (b) Primary allogeneic MLR of granuloma-derived liver LD cells, normal liver LD cells, spleen LD cells, and responder cells alone. Three mice per group and 1,000 total cells/smear were examined. Representative data from six experiments. Mean ± SD (n = 3).
Mentions: Mice exposed to P. acnes by day 7 developed numerous granulomas in the liver (20; Fig. 1, a–g). F4/80+ cells including Kupffer cells and inflammatory macrophages 28 were evenly distributed throughout the granulomas (Fig. 1 f), whereas CD4+ cells localized in the periphery (Fig. 1 c). In addition, cells with the markers of DCs 11926, such as CD11c, DEC-205, M342, MHC class II, and CD86, were also distributed within granulomas (Fig. 1, a–e). We then investigated LD cells recovered on Nycodenz gradients from the NPC fraction of a granulomatous liver. A majority of LD cells actually had features of DCs, such as an eccentric irregular nucleus and a cytoplasmic membrane with ruffled projections (data not shown). The cells were MHC class IIhigh, CD11c+, DEC-205+, ICAM-1+, CD3ε−, B220−, CD8α−, Gr-1−, and expressed moderate levels of CD86, LFA-1, and CD11b (Fig. 2 a). In a functional study, they induced considerable proliferation of allogeneic T cells in vitro, compared with normal liver- and spleen-derived LD cells (Fig. 2 b), demonstrating that the granuloma contained functionally mature DCs. Moreover, DEC-205+ cells were in close contact with CD4+ T cells, many of which were in a proliferative stage, as evidenced by in situ BrdU labeling (Fig. 1 c). This suggests that DCs in the granuloma have potent antigen-presenting function and can activate T cells in situ.

Bottom Line: 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).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