Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7-induced immune activation in rheumatoid arthritis.
OBJECTIVE
To evaluate the expression and functional ability of the high-affinity interleukin-7 receptor (IL-7Ralpha) in patients with rheumatoid arthritis (RA).


METHODS
Expression of IL-7Ralpha and IL-7 was determined in synovial tissue from RA patients and was compared with that in synovial tissue from patients with undifferentiated arthritis (UA) and osteoarthritis (OA). IL-7Ralpha expression on CD4 T cells, CD19 B cells, and CD14 monocyte/macrophages from RA synovial tissue, synovial fluid, and peripheral blood was also assessed. The proliferative capacity of IL-7Ralpha(bright) and IL-7Ralpha(dim/-) T cells was measured. In addition, we examined IL-7R blockade with soluble human IL-7Ralpha (hIL-7Ralpha) in the prevention of immune activation of peripheral blood mononuclear cells.


RESULTS
We found significantly higher IL-7Ralpha expression in RA and UA synovial tissue than in OA synovial tissue, and the level of IL-7Ralpha expression correlated significantly with the levels of CD3 and IL-7 expression. CD4 T cells from RA synovial fluid and synovial tissue strongly expressed IL-7Ralpha. A substantial percentage of B cells and macrophages from RA synovial fluid and synovial tissue also expressed IL-7Ralpha, although less prominently than T cells. We found that peripheral blood IL-7Ralpha(bright) T cells that did not express FoxP3 were highly proliferative as compared with IL-7Ralpha(dim/-) T cells that did express high levels of FoxP3. Soluble hIL-7Ralpha inhibited IL-7-induced proliferation and interferon-gamma production by mononuclear cells from RA patients.


CONCLUSIONS
Our data suggest that enhanced expression of IL-7Ralpha and IL-7 in RA patients contributes significantly to the joint inflammation by activating T cells, B cells, and macrophages. The inhibition of IL-7R-mediated immune activation by soluble hIL-7Ralpha further indicates an important role of IL-7Ralpha in inflammatory responses in RA, suggesting IL-7Ralpha as a therapeutic target for immunotherapy in RA.
Hartgring
Sarita A Y
SA
Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
van Roon
Joel A G
JA
Wenting-van Wijk
Marion
M
Jacobs
Kim M G
KM
Jahangier
Zalima N
ZN
Willis
Cynthia R
CR
Bijlsma
Johannes W J
JW
Lafeber
Floris P J G
FP
D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000378:metabolism; D001168:Arthritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism*; D007596:Joints / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D018941:Antigens, CD19; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015851:Interleukin-7; D018950:Lipopolysaccharide Receptors; D020395:Receptors, Interleukin-7