| First Author | Santiago ML | Year | 1997 |
| Journal | J Exp Med | Volume | 185 |
| Issue | 1 | Pages | 65-70 |
| PubMed ID | 8996242 | Mgi Jnum | J:37574 |
| Mgi Id | MGI:84965 | Doi | 10.1084/jem.185.1.65 |
| Citation | Santiago ML, et al. (1997) Interleukin-4 protects against a genetically linked lupus-like autoimmune syndrome. J Exp Med 185(1):65-70 |
| abstractText | 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. |
