PMID- 22006377
OWN - NLM
STAT- MEDLINE
DCOM- 20120914
LR  - 20120329
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 64
IP  - 4
DP  - 2012 Apr
TI  - CXCR3 promotes the production of IgG1 autoantibodies but is not essential for the 
      development of lupus nephritis in NZB/NZW mice.
PG  - 1237-46
LID - 10.1002/art.33424 [doi]
AB  - OBJECTIVE: Autoantibody immune complexes and cellular infiltrates drive nephritis 
      in patients with systemic lupus erythematosus (SLE) and in murine lupus. The 
      chemokine receptor CXCR3 is assumed to promote cellular infiltration of inflamed 
      tissues. Moreover, CXCR3 deficiency ameliorates lupus nephritis in the 
      MRL/MpJ-Fas(lpr) (MRL/lpr) mouse model of SLE. Hence, CXCR3 blockade has been 
      suggested as a novel therapeutic strategy for the treatment of lupus nephritis. 
      We undertook this study to test the effect of CXCR3 in the (NZB x NZW)F(1) 
      (NZB/NZW) mouse model of SLE. METHODS: CXCR3(-/-) NZB/NZW mice were generated and 
      monitored for survival, proteinuria, and kidney infiltration. 
      Anti-double-stranded DNA (anti-dsDNA) and total IgG1, IgG2a, and IgG2b antibody 
      levels were determined by enzyme-linked immunosorbent assay. T cell and plasma 
      cell infiltrates in the kidneys and interferon-gamma production were determined by 
      flow cytometry. Plasma cell infiltrates were measured using enzyme-linked 
      immunospot assay. Kidney tissue was evaluated for pathologic changes. RESULTS: 
      CXCR3(-/-) NZB/NZW mice exhibited reduced production of total and anti-dsDNA 
      antibodies of the IgG1 subclass, but had normal titers of IgG2a and IgG2b 
      antibodies compared to CXCR3(+/+) NZB/NZW mice. Cellular infiltrates and 
      glomerulonephritis were not reduced in CXCR3(-/-) mice. CONCLUSION: CXCR3 has an 
      effect on (auto)antibody production but is not essential for lupus pathogenesis 
      in NZB/NZW mice, indicating that the effect of CXCR3 on the development of kidney 
      disease varies between MRL/lpr and NZB/NZW mice. These results suggest that 
      CXCR3-dependent and -independent mechanisms can mediate lupus nephritis. Hence, 
      therapeutic CXCR3 blockade could be beneficial for only a subgroup of patients 
      with SLE.
CI  - Copyright (c) 2012 by the American College of Rheumatology.
FAU - Moser, Katrin
AU  - Moser K
AD  - University of Lubeck, Lubeck, Germany.
FAU - Kalies, Kathrin
AU  - Kalies K
FAU - Szyska, Martin
AU  - Szyska M
FAU - Humrich, Jens Y
AU  - Humrich JY
FAU - Amann, Kerstin
AU  - Amann K
FAU - Manz, Rudolf A
AU  - Manz RA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111017
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, CXCR3)
SB  - IM
MH  - Animals
MH  - Antigen-Antibody Complex/immunology
MH  - Autoantibodies/*immunology
MH  - Immunoglobulin G/*immunology
MH  - Lupus Nephritis/immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred NZB
MH  - Proteinuria/immunology/metabolism
MH  - Receptors, CXCR3/*metabolism
MH  - T-Lymphocytes/immunology/metabolism
EDAT- 2011/10/19 06:00
MHDA- 2012/09/15 06:00
CRDT- 2011/10/19 06:00
PHST- 2011/10/19 06:00 [entrez]
PHST- 2011/10/19 06:00 [pubmed]
PHST- 2012/09/15 06:00 [medline]
AID - 10.1002/art.33424 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2012 Apr;64(4):1237-46. doi: 10.1002/art.33424. Epub 2011 Oct 
      17.