TY - JOUR
T1 - Loss of IL-22 inhibits autoantibody formation in collagen-induced arthritis in mice
AU - Corneth, Odilia B.J.
AU - Reijmers, Rogier M.
AU - Mus, Adriana M.C.
AU - Asmawidjaja, Patrick S.
AU - van Hamburg, Jan Piet
AU - Papazian, Natalie
AU - Siegers, Jurre Y.
AU - Mourcin, Frédéric
AU - Amin, Rada
AU - Tarte, Karin
AU - Hendriks, Rudi W.
AU - Cupedo, Tom
AU - Lubberts, Erik
N1 - Funding Information: We would like to thank Dr. W. Ouyang (Genentech, Inc) for kindly providing the IL-22 Publisher Copyright: © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Interleukin 22 (IL-22) expression is associated with increased joint destruction and disease progression in rheumatoid arthritis (RA). Although IL-22 is considered a pro-inflammatory cytokine, its mechanism of action in RA remains incompletely understood. Here, we used the collagen-induced arthritis model in IL-22 deficient (IL-22−/−) mice to study the role of IL-22 in RA. In spite of normal disease incidence, disease severity is significantly diminished in IL-22−/− mice. Moreover, pathogenicity of Th17 cells and development and function of B cells are unaffected. In contrast, splenic plasma cells, as well as serum autoantibody titers, are reduced in the absence of IL-22. At the peak of disease, germinal centers (GCs) are severely reduced in the spleens of IL-22−/− mice, correlating with a decline in GC B-cell numbers. Within the GC, we identified IL-22R1 expressing follicular dendritic cell-like stromal cells. Human lymphoid stromal cells respond to IL-22 ex vivo by inducing transcription of CXCL12 and CXCL13. We therefore postulate IL-22 as an important enhancer of the GC reaction, maintaining chemokine levels for the persistence of GC reactions, essential for the production of autoantibody-secreting plasma cells. Blocking IL-22 might therefore prevent immune-complex deposition and destruction of joints in RA patients.
AB - Interleukin 22 (IL-22) expression is associated with increased joint destruction and disease progression in rheumatoid arthritis (RA). Although IL-22 is considered a pro-inflammatory cytokine, its mechanism of action in RA remains incompletely understood. Here, we used the collagen-induced arthritis model in IL-22 deficient (IL-22−/−) mice to study the role of IL-22 in RA. In spite of normal disease incidence, disease severity is significantly diminished in IL-22−/− mice. Moreover, pathogenicity of Th17 cells and development and function of B cells are unaffected. In contrast, splenic plasma cells, as well as serum autoantibody titers, are reduced in the absence of IL-22. At the peak of disease, germinal centers (GCs) are severely reduced in the spleens of IL-22−/− mice, correlating with a decline in GC B-cell numbers. Within the GC, we identified IL-22R1 expressing follicular dendritic cell-like stromal cells. Human lymphoid stromal cells respond to IL-22 ex vivo by inducing transcription of CXCL12 and CXCL13. We therefore postulate IL-22 as an important enhancer of the GC reaction, maintaining chemokine levels for the persistence of GC reactions, essential for the production of autoantibody-secreting plasma cells. Blocking IL-22 might therefore prevent immune-complex deposition and destruction of joints in RA patients.
KW - Autoantibody formation
KW - B cell
KW - Germinal center
KW - Interleukin 22 (IL-22)
KW - Rheumatoid arthritis
UR - http://www.scopus.com/inward/record.url?scp=84973663355&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/eji.201546241
DO - https://doi.org/10.1002/eji.201546241
M3 - Article
C2 - 27067635
SN - 0014-2980
VL - 46
SP - 1404
EP - 1414
JO - European journal of immunology
JF - European journal of immunology
IS - 6
ER -