The alpha 1 beta 1 and alpha E beta 7 integrins define a subset of dendritic cells in peripheral lymph nodes with unique adhesive and antigen uptake properties.
Dendritic cells (DCs) are a heterogeneous population of APCs with critical roles in T cell activation and immune regulation. We report in this study the identification and characterization of a novel subset of DCs resident in skin-draining peripheral lymph nodes of normal mice. This subset of CD11c(high)CD40(high)CD8alpha(intermediate (int)) DCs expresses the collagen-binding integrin, alpha1beta1, and the E-cadherin-binding integrin, alphaEbeta7. Although alpha1beta1 and alphaEbeta7 are also expressed on CD11c(high)CD40(int)CD8alpha(high) lymphoid DCs, CD11c(high)CD40(high)CD8alpha(int) DCs demonstrate preferential integrin-mediated adhesion to collagen and fibronectin. This DC subset most likely acquires expression of these integrins in peripheral lymph node, as this subset is not found in the spleen or mesenteric lymph node, and recent DC migrants from the skin lack expression of alpha1beta1 and alphaEbeta7 integrins. Resident CD40(high) DCs express alpha1beta1 integrin and colocalize with collagen in lymph nodes. When compared with CD11c(high)CD40(high)CD8alpha(int) DCs lacking expression of these integrins, the alpha1beta1+alphaEbeta7+DC subset exhibits more efficient formation of Ag-independent conjugates with T cells, and a decreased ability to acquire soluble Ag. Thus, the alpha1beta1 and alphaEbeta7 integrins define a unique population of peripheral lymph node-derived DCs with altered functional properties and adhesive potential that localizes these cells to sites in lymph nodes where Ag presentation to T cells occurs.
Pribila
Jonathan T
JT
Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Itano
Andrea A
AA
Mueller
Kristen L
KL
Shimizu
Yoji
Y
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D039521:CD11c Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003094:Collagen / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D016130:Immunophenotyping; D039222:Integrin alpha1beta1 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D039421:Integrin alpha2 / Q000378:metabolism; D016023:Integrins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011485:Protein Binding / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012995:Solubility
D000941:Antigens; D039521:CD11c Antigen; D019013:CD40 Antigens; D016827:CD8 Antigens; C431698:CD8alpha antigen; D015820:Cadherins; D018984:Epitopes, T-Lymphocyte; D005353:Fibronectins; D039222:Integrin alpha1beta1; D039421:Integrin alpha2; D016023:Integrins; C070709:integrin alphaEbeta7; D003094:Collagen