Cellular distribution of the C-type II lectin dendritic cell immunoreceptor (DCIR) and its expression in the rheumatic joint: identification of a subpopulation of DCIR+ T cells.
OBJECTIVE
An association to variations in the dendritic cell immunoreceptor (DCIR) gene with rheumatoid arthritis (RA) was recently shown. However, protein expression of DCIR has so far not been assessed in a disease setting. In the present work, we aimed to determine the cellular and tissue distribution of this receptor in healthy controls and in patients with RA before and after local glucocorticoid administration.


METHODS
DCIR mRNA expression was evaluated by quantitative PCR (n=3) and protein expression by flow cytometry (n=18), immunohistochemistry (n=14) and double immunofluorescence (n=5).


RESULTS
DCIR protein was not detected in healthy synovia. By contrast, expression was abundant on cells from rheumatic joints in synovial fluid and in tissue. Following corticosteroid treatment this expression was downregulated. Interestingly, DCIR could be detected on natural killer (NK) cells and T cells, and CD4+ and CD8+, as well as on monocytes, B cells, dendritic cells and granulocytes. The frequency of DCIR+ T cells and the level of surface expression were increased in the rheumatic joint compared to blood. In synovial fluid the typical DCIR+ T cells were large activated cells, whereas blasted DCIR+ T cells were not detected in blood.


CONCLUSIONS
We demonstrate increased protein and mRNA expression of DCIR in RA, especially in the rheumatic joint. Expression was widespread and included a subpopulation of T cells. This suggests that the inflammatory synovial environment induces DCIR expression, and this may be related to synovial T cell function. Ligation of DCIR, or lack thereof, could contribute to the chronic inflammation characterising autoimmune diseases such as RA.
Eklöw
C
C
Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Makrygiannakis
D
D
Bäckdahl
L
L
Padyukov
L
L
Ulfgren
A-K
AK
Lorentzen
J C
JC
Malmström
V
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D055815:Young Adult
C423004:CLEC4A protein, human; D005938:Glucocorticoids; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic