Journal article
IL-21 promotes the production of anti-DNA IgG but is dispensable for kidney damage in lyn−/− mice
European journal of immunology, Vol.43(2), pp.382-393
02/2013
DOI: 10.1002/eji.201142095
PMCID: PMC3768150
PMID: 23169140
Abstract
The autoimmune disease systemic lupus erythematosus (SLE) is characterized by loss of tolerance to nuclear antigens and a heightened inflammatory environment, which together result in end organ damage. Lyn-deficient mice, a model of SLE, lack an inhibitor of B- and myeloid cell activation. This results in B-cell hyperresponsiveness, plasma cell (PC) accumulation, autoantibodies, and glomerulonephritis (GN). IL-21 is associated with autoimmunity in mice and humans and promotes B-cell differentiation and class switching. Here, we explore the role of IL-21 in the autoimmune phenotypes of lyn−/−mice. We find that IL-21 mRNA is reduced in the spleens of lyn−/−IL-6 −/− and lyn−/− Btk lo mice, neither of which produce pathogenic autoantibodies or develop significant GN. While IL-21 is dispensable for PC accumulation and IgM autoantibodies in lyn−/− mice, it is required for anti-DNA IgG antibodies and some aspects of T cell activation. Surprisingly, GN still develops in lyn−/−IL-21 −/− mice. This likely results from the presence of IgG autoantibodies against a limited set of non-DNA antigens. These studies identify a specific role for IL-21 in the class switching of anti-DNA B-cells and demonstrate that neither IL-21 nor anti-DNA IgG is required for kidney damage in lyn −/− mice.
Details
- Title: Subtitle
- IL-21 promotes the production of anti-DNA IgG but is dispensable for kidney damage in lyn−/− mice
- Creators
- Toni Gutierrez - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USAJessica M Mayeux - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USASterling B Ortega - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USANitin J Karandikar - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USAQuan-Zhen Li - Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USADinesh Rakheja - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USAXin J Zhou - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USAAnne B Satterthwaite - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Resource Type
- Journal article
- Publication Details
- European journal of immunology, Vol.43(2), pp.382-393
- DOI
- 10.1002/eji.201142095
- PMID
- 23169140
- PMCID
- PMC3768150
- ISSN
- 0014-2980
- eISSN
- 1521-4141
- Grant note
- P01 AI039824 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Language
- English
- Date published
- 02/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984047611202771
Metrics
14 Record Views