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

2000 ◽  
Vol 193 (1) ◽  
pp. 35-50 ◽  
Author(s):  
Hiroyuki Yoneyama ◽  
Kenjiro Matsuno ◽  
Yanyun Zhang ◽  
Masako Murai ◽  
Meiji Itakura ◽  
...  

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 1α 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.

1997 ◽  
Vol 186 (6) ◽  
pp. 837-844 ◽  
Author(s):  
David R. Greaves ◽  
Wei Wang ◽  
Daniel J. Dairaghi ◽  
Marie Caroline Dieu ◽  
Blandine de Saint-Vis ◽  
...  

Dendritic cells initiate immune responses by ferrying antigen from the tissues to the lymphoid organs for presentation to lymphocytes. Little is known about the molecular mechanisms underlying this migratory behavior. We have identified a chemokine receptor which appears to be selectively expressed in human dendritic cells derived from CD34+ cord blood precursors, but not in dendritic cells derived from peripheral blood monocytes. When stably expressed as a recombinant protein in a variety of host cell backgrounds, the receptor shows a strong interaction with only one chemokine among 25 tested: the recently reported CC chemokine macrophage inflammatory protein 3α. Thus, we have designated this receptor as the CC chemokine receptor 6. The cloning and characterization of a dendritic cell CC chemokine receptor suggests a role for chemokines in the control of the migration of dendritic cells and the regulation of dendritic cell function in immunity and infection.


Blood ◽  
1999 ◽  
Vol 93 (10) ◽  
pp. 3233-3240 ◽  
Author(s):  
Karin Franz-Bacon ◽  
Daniel J. Dairaghi ◽  
Stefen A. Boehme ◽  
Susan K. Sullivan ◽  
Thomas J. Schall ◽  
...  

Eotaxin has been characterized as a chemokine involved in eosinophil activation; however, mRNA for this C-C chemokine has been shown to be constitutively expressed in thymus. Immunohistochemical analysis showed a punctate distribution pattern, with eotaxin expression localized mainly in the medulla and in Hassle’s corpuscles. Moreover, the receptor for eotaxin, CCR-3, was detected on thymocytes, with the highest level of expression being on the CD8 single-positive population. Equilibrium binding analyses on unfractionated thymocytes demonstrated specific 125I-eotaxin binding profiles comparable with CCR-3 transfectants. Eotaxin induced cell migration and mobilization of intracellular calcium in all thymocytes except the immature CD4−/CD8− population. Eotaxin also induced the secretion of the chemokines interleukin-8, RANTES, and macrophage inflammatory protein-1β from thymocyte cultures in vitro. These results suggest that eotaxin-induced thymocyte activation may have important physiological implications for lymphocyte mobilization within and from this lymphoid organ.


2000 ◽  
Vol 191 (8) ◽  
pp. 1381-1394 ◽  
Author(s):  
Akiko Iwasaki ◽  
Brian L. Kelsall

We describe the anatomical localization of three distinct dendritic cell (DC) subsets in the murine Peyer's patch (PP) and explore the role of chemokines in their recruitment. By two-color in situ immunofluorescence, CD11b+ myeloid DCs were determined to be present in the subepithelial dome (SED) region, whereas CD8α+ lymphoid DCs are present in the T cell–rich interfollicular region (IFR). DCs that lack expression of CD8α or CD11b (double negative) are present in both the SED and IFR. By in situ hybridization, macrophage inflammatory protein (MIP)-3α mRNA was dramatically expressed only by the follicle-associated epithelium overlying the SED, while its receptor, CCR6, was concentrated in the SED. In contrast, CCR7 was expressed predominantly in the IFR. Consistent with these findings, reverse transcriptase polymerase chain reaction analysis and in vitro chemotaxis assays using freshly isolated DCs revealed that CCR6 was functionally expressed only by DC subsets present in the SED, while all subsets expressed functional CCR7. Moreover, none of the splenic DC subsets migrated toward MIP-3α. These data support a distinct role for MIP-3α/CCR6 in recruitment of CD11b+ DCs toward the mucosal surfaces and for MIP-3β/CCR7 in attraction of CD8α+ DCs to the T cell regions. Finally, we demonstrated that all DC subsets expressed an immature phenotype when freshly isolated and maintained expression of subset markers upon maturation in vitro. In contrast, CCR7 expression by myeloid PP DCs was enhanced with maturation in vitro. In addition, this subset disappeared from the SED and appeared in the IFR after microbial stimulation in vivo, suggesting that immature myeloid SED DCs capture antigens and migrate to IFR to initiate T cell responses after mucosal microbial infections.


2003 ◽  
Vol 123 (1) ◽  
pp. 106-109 ◽  
Author(s):  
Evangelos Terpos ◽  
Marianna Politou ◽  
Richard Szydlo ◽  
John M. Goldman ◽  
Jane F. Apperley ◽  
...  

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