Characterization of the Expression and Function of the C-Type Lectin Receptor CD302 in Mice and Humans Reveals a Role in Dendritic Cell Migration.
C-type lectin receptors play important roles in immune cell interactions with the environment. We described CD302 as the simplest, single domain, type I C-type lectin receptor and showed it was expressed mainly on the myeloid phagocytes in human blood. CD302 colocalized with podosomes and lamellopodia structures, so we hypothesized that it played a role in cell adhesion or migration. In this study, we used mouse models to obtain further insights into CD302 expression and its potential immunological function. Mouse CD302 transcripts were, as in humans, highest in the liver, followed by lungs, lymph nodes (LN), spleen, and bone marrow. In liver, CD302 was expressed by hepatocytes, liver sinusoidal endothelial cells, and Kupffer cells. A detailed analysis of CD302 transcription in mouse immune cells revealed highest expression by myeloid cells, particularly macrophages, granulocytes, and myeloid dendritic cells (mDC). Interestingly, 2.5-fold more CD302 was found in migratory compared with resident mDC populations and higher CD302 expression in mouse M1 versus M2 macrophages was also noteworthy. CD302 knockout (CD302KO) mice were generated. Studies on the relevant immune cell populations revealed a decrease in the frequency and numbers of migratory mDC within CD302KO LN compared with wild-type LN. In vitro studies showed CD302KO and wild-type DC had an equivalent capacity to undergo maturation, prime T cells, uptake Ags, and migrate toward the CCL19/CCL21 chemokines. Nevertheless, CD302KO migratory DC exhibited reduced in vivo migration into LN, confirming a functional role for CD302 in mDC migration.
Dendritic Cell Research, ANZAC Research Institute, Sydney, New South Wales 2139, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia;
Tsun-Ho
0000-0003-0229-6004
TH
Lo
Dendritic Cell Research, ANZAC Research Institute, Sydney, New South Wales 2139, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia;
Pablo A
0000-0001-5074-8824
PA
Silveira
Dendritic Cell Research, ANZAC Research Institute, Sydney, New South Wales 2139, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia;
Phillip D
0000-0001-7047-1113
PD
Fromm
Dendritic Cell Research, ANZAC Research Institute, Sydney, New South Wales 2139, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia;
Nirupama D
ND
Verma
Dendritic Cell Research, ANZAC Research Institute, Sydney, New South Wales 2139, Australia;
Phi A
PA
Vu
Dendritic Cell Research, ANZAC Research Institute, Sydney, New South Wales 2139, Australia;
Fiona
F
Kupresanin
Dendritic Cell Research, ANZAC Research Institute, Sydney, New South Wales 2139, Australia;
Rhonda
R
Adam
Mater Medical Research Institute, Brisbane, Queensland 4101, Australia;
Masato
0000-0002-6041-6804
M
Kato
Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia; Biogerontology Laboratory, ANZAC Research Institute, Sydney, New South Wales 2139, Australia; and.
Victoria C
0000-0002-6346-9928
VC
Cogger
Dendritic Cell Research, ANZAC Research Institute, Sydney, New South Wales 2139, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia;
Georgina J
0000-0001-7894-232X
GJ
Clark
Dendritic Cell Research, ANZAC Research Institute, Sydney, New South Wales 2139, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia; Department of Haematology, Royal Prince Alfred Hospital, Sydney, New South Wales 2050, Australia derek.hart@sydney.edu.au.
Derek N J
0000-0003-2620-1612
DN
Hart
D000818:Animals; D002460:Cell Line; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003713:Dendritic Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism*
C477741:CD302 protein, human; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface