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

Effect of anti-SLC pAb on liver injury and PALT. (a) CD11c+ cells (red) surround the necrotic area at 7 d after treatment with anti-SLC pAb. Type IV collagen (brown). Original magnification: ×100. (b) Serum ALT levels on day 7. (c) The absolute numbers of CD11c+ NPCs. (d and e) The numbers of BrdU+CD4+ and B220+ cells in the PALT and sinusoidal granulomatous (GR) area, and BrdU+ and DEC205+ cells in the paracortex of hepatic LNs determined by 15 mm2 stained cryosections on day 7. T cell area of hepatic LNs was defined by B220 or CD3ε staining. (f) The absolute numbers and primary allogeneic MLR of LD-DCs from anti-SLC pAb and control Ab–treated mice (day 7). Representative data from six independent experiments. Mean ± SD (n = 3). Asterisk, P < 0.05.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2195882&req=5

Figure 10: Effect of anti-SLC pAb on liver injury and PALT. (a) CD11c+ cells (red) surround the necrotic area at 7 d after treatment with anti-SLC pAb. Type IV collagen (brown). Original magnification: ×100. (b) Serum ALT levels on day 7. (c) The absolute numbers of CD11c+ NPCs. (d and e) The numbers of BrdU+CD4+ and B220+ cells in the PALT and sinusoidal granulomatous (GR) area, and BrdU+ and DEC205+ cells in the paracortex of hepatic LNs determined by 15 mm2 stained cryosections on day 7. T cell area of hepatic LNs was defined by B220 or CD3ε staining. (f) The absolute numbers and primary allogeneic MLR of LD-DCs from anti-SLC pAb and control Ab–treated mice (day 7). Representative data from six independent experiments. Mean ± SD (n = 3). Asterisk, P < 0.05.

Mentions: To define the biological role of SLC in granuloma formation, we investigated the effect of anti-SLC pAb on granuloma-associated liver injury. Mice were injected with anti-SLC pAb 0 and 2 d after P. acnes treatment. At day 7, anti-SLC pAb unexpectedly enhanced sinusoidal granuloma formation and hepatocellular damage (Fig. 10, a and b). In some cases, limited hepatocellular necrosis was observed surrounding the granulomatous area (Fig. 10 a). CD11c+ NPCs were increased in number by treatment with anti-SLC pAb (Fig. 10 c), but they decreased in the portal area. This may be due to an interference with movement of CD11c+ DCs into the portal area, but without any affect on the entry of blood CD11c+ DC precursor into the liver sinusoid. Thus, CD11c+ cells selectively increased in number in the sinusoidal granulomatous area and sometimes at the margin of the necrotic area. In contrast, BrdU+ and B220+ cells were reduced in number (Fig. 10 d) and the HEV-like vessels could not be seen in the portal area (data not shown), supporting the inhibitory role of anti-SLC pAb on induction of PALT. This means anti-SLC pAb treatment reduced PALT expansion, but enhanced sinusoidal granuloma formation. BrdU+ and DEC-205+ cells were also decreased in number in the T cell areas of hepatic LNs, after anti-SLC Ab treatment (Fig. 10 e), suggesting that mature DEC-205+ DCs failed to migrate to the regional LNs via draining lymphatics and that naive CD4+ T cells also failed to enter the LNs via HEVs from the circulation 6. As a consequence, cluster formation between mature DCs and naive T cells within PALT and regional LNs were decreased, leading to impaired primary T cell proliferative responses. Most of the granuloma-derived LD DCs obtained from anti-SLC pAb–treated liver showed low allostimulatory capability (Fig. 10 f), suggesting that immobilized DCs within granulomas did not undergo functional maturation. The reduction in number of BrdU+CD4+ T cells in the sinusoidal area (Fig. 10 d) also supported this idea. Therefore, effective immune responses were impaired not only locally but also at regional LN levels.


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)

Effect of anti-SLC pAb on liver injury and PALT. (a) CD11c+ cells (red) surround the necrotic area at 7 d after treatment with anti-SLC pAb. Type IV collagen (brown). Original magnification: ×100. (b) Serum ALT levels on day 7. (c) The absolute numbers of CD11c+ NPCs. (d and e) The numbers of BrdU+CD4+ and B220+ cells in the PALT and sinusoidal granulomatous (GR) area, and BrdU+ and DEC205+ cells in the paracortex of hepatic LNs determined by 15 mm2 stained cryosections on day 7. T cell area of hepatic LNs was defined by B220 or CD3ε staining. (f) The absolute numbers and primary allogeneic MLR of LD-DCs from anti-SLC pAb and control Ab–treated mice (day 7). Representative data from six independent experiments. Mean ± SD (n = 3). Asterisk, P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 10: Effect of anti-SLC pAb on liver injury and PALT. (a) CD11c+ cells (red) surround the necrotic area at 7 d after treatment with anti-SLC pAb. Type IV collagen (brown). Original magnification: ×100. (b) Serum ALT levels on day 7. (c) The absolute numbers of CD11c+ NPCs. (d and e) The numbers of BrdU+CD4+ and B220+ cells in the PALT and sinusoidal granulomatous (GR) area, and BrdU+ and DEC205+ cells in the paracortex of hepatic LNs determined by 15 mm2 stained cryosections on day 7. T cell area of hepatic LNs was defined by B220 or CD3ε staining. (f) The absolute numbers and primary allogeneic MLR of LD-DCs from anti-SLC pAb and control Ab–treated mice (day 7). Representative data from six independent experiments. Mean ± SD (n = 3). Asterisk, P < 0.05.
Mentions: To define the biological role of SLC in granuloma formation, we investigated the effect of anti-SLC pAb on granuloma-associated liver injury. Mice were injected with anti-SLC pAb 0 and 2 d after P. acnes treatment. At day 7, anti-SLC pAb unexpectedly enhanced sinusoidal granuloma formation and hepatocellular damage (Fig. 10, a and b). In some cases, limited hepatocellular necrosis was observed surrounding the granulomatous area (Fig. 10 a). CD11c+ NPCs were increased in number by treatment with anti-SLC pAb (Fig. 10 c), but they decreased in the portal area. This may be due to an interference with movement of CD11c+ DCs into the portal area, but without any affect on the entry of blood CD11c+ DC precursor into the liver sinusoid. Thus, CD11c+ cells selectively increased in number in the sinusoidal granulomatous area and sometimes at the margin of the necrotic area. In contrast, BrdU+ and B220+ cells were reduced in number (Fig. 10 d) and the HEV-like vessels could not be seen in the portal area (data not shown), supporting the inhibitory role of anti-SLC pAb on induction of PALT. This means anti-SLC pAb treatment reduced PALT expansion, but enhanced sinusoidal granuloma formation. BrdU+ and DEC-205+ cells were also decreased in number in the T cell areas of hepatic LNs, after anti-SLC Ab treatment (Fig. 10 e), suggesting that mature DEC-205+ DCs failed to migrate to the regional LNs via draining lymphatics and that naive CD4+ T cells also failed to enter the LNs via HEVs from the circulation 6. As a consequence, cluster formation between mature DCs and naive T cells within PALT and regional LNs were decreased, leading to impaired primary T cell proliferative responses. Most of the granuloma-derived LD DCs obtained from anti-SLC pAb–treated liver showed low allostimulatory capability (Fig. 10 f), suggesting that immobilized DCs within granulomas did not undergo functional maturation. The reduction in number of BrdU+CD4+ T cells in the sinusoidal area (Fig. 10 d) also supported this idea. Therefore, effective immune responses were impaired not only locally but also at regional LN levels.

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