IL-4 and many roads to lupuslike autoimmunity.
Interleukin-4 (IL-4) is a multifunctional cytokine. Although most studies have focused on the B-cell stimulatory and Th2 promoting properties of IL-4 in the development of autoantibodies and autoantibody-mediated diseases, a few reports suggest a T-cell suppressor role for this cytokine in lupus. Since these properties of IL-4 may sometimes result in opposing outcomes, amplifying or inhibitory, on overall B-cell functions, it is not surprising that a few studies have found no role for IL-4 in the development of autoantibodies and lupus. Evidence for a more novel role for IL-4 in the development of lupus nephritis comes from recent studies, which suggests that IL-4 may directly promote extracellular matrix deposition in the glomeruli. Consistent with this idea, blockade of IL-4 by antibody treatment or of its signaling by inactivation of the Stat6 gene ameliorates glomerulosclerosis and delays or even prevents the development of end-stage renal disease, despite the presence of high levels of IgG anti-dsDNA Antibodies. Thus, IL-4 may serve multiple roles in the development of lupus: it may enhance autoantibody production via its direct B-cell effects, protect against autoimmunity via its T-cell suppressor effect, or perpetuate tissue damage via its direct effects on target organs.
Singh
Ram Raj
RR
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015536:Down-Regulation; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology*; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D016207:Cytokines; D015847:Interleukin-4