en
Scientific article
English

Interleukin-4 protects against a genetically linked lupus-like autoimmune syndrome

Published inThe Journal of experimental medicine, vol. 185, no. 1, p. 65-70
Publication date1997
Abstract

Interleukin-4 (IL-4) provides support for humoral immune responses through upregulation of T helper (Th) type 2 cell differentiation, but it is not known whether IL-4 promotes antibody-mediated autoimmune diseases such as systemic lupus erythematosus (SLE). Here, we show that the constitutive expression of an IL-4 transgene by B cells completely prevents the development of lethal lupus-like glomerulonephritis in the (NZW x C57BL/6.Yaa)F1 murine model of SLE. This was associated with marked changes in the serum levels of IgG subclasses, rather than in the total levels of anti-DNA antibodies, with a lack of IgG3, a decrease of IgG2a, and an increase in IgG1 subclasses, and by a strong reduction in the serum levels of gp70-anti-gp70 immune complexes. This effect of the transgene appears to result from a modulation of the Th1 versus Th2 autoimmune response, since the protected mice displayed comparably modified IgG2a and IgG3 antibody response against exogenous T cell-dependent antigen, but not against T cell-independent antigens. Thus, IL-4 prevents the development of this lupus-like autoimmune disease, most likely by downregulating the appearance of Th1-mediated IgG subclasses of autoantibodies such as the IgG3 autoantibodies which have been shown to be especially nephritogenic.

Keywords
  • Animals
  • Antibodies, Antinuclear/biosynthesis/blood
  • Antibody Formation
  • B-Lymphocytes/ immunology
  • Cell Differentiation
  • Enhancer Elements, Genetic
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immunoglobulin G/blood
  • Immunoglobulin Heavy Chains/genetics
  • Interleukin-4/ biosynthesis/genetics
  • Lupus Nephritis/ genetics/immunology/ prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • T-Lymphocytes/immunology
  • Th2 Cells/cytology/immunology
Affiliation Not a UNIGE publication
Citation (ISO format)
SANTIAGO-RABER, Marie-Laure et al. Interleukin-4 protects against a genetically linked lupus-like autoimmune syndrome. In: The Journal of experimental medicine, 1997, vol. 185, n° 1, p. 65–70. doi: 10.1084/jem.185.1.65
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ISSN of the journal0022-1007
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