| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T02318 | ||||
| Target Name | Tumor necrosis factor ligand superfamily member 13B | ||||
| Target Type | Successful |
||||
| Drug Potency against Target | Belimumab | Drug Info | EC50 = 560 nM | [552910] | |
| Action against Disease Model | Atacicept | Atacicept is a h uMan recombinant fusion protein that comprises the binding portion of a receptor for both BLyS (B-Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), two cytokines that have been identified as important regulators of B-cell maturation, function and survival. Atacicept has shown selective effects on cells of the B-cell lineage, acting on mature B cells and blocking plasma cells and late stages of B-cell development while sparing B-cell progenitors and memory cells. The efficacy of atacicept in animal models of autoimmune disease and the biological activity of atacicept in patients with systemic lupus erythematosus (SLE) and rhe uMatoid arthritis (RA) has been demonstrated. | [553084] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | Using Lyn-deficient mice, we show that overproduction of BAFF by hyperactive myeloid cells contributes to inflammation and autoimmunity in part by acting directly on T cells to induce the release of IFN-gamma. Genetic deletion of IFN-gamma or reduction of BAFF activity, achieved by either reducing myeloid cell hyperproduction or by treating with an anti-BAFF monoclonal antibody, reduced disease development in lyn(-/-) mice. The increased production of IFN-gamma in lyn(-/-) mice feeds back on the myeloid cells to further stimulate BAFF release. Expression of B lymphocyte stimulator receptor on T cells was required for their full activation and IFN-gamma release. Overall, our data suggest that the reciprocal production of BAFF and IFN-gamma establishes an inflammatory loop between myeloid cells and T cells that exacerbates autoimmunity in this model. Our findings uncover an important pathological role of BAFF in autoimmune disorders. | [553084] | |||
| References | |||||
| Ref 553084 | Atacicept: targeting B cells in multiple sclerosis. Ther Adv Neurol Disord. 2010 Jul;3(4):205-16. doi: 10.1177/1756285610371146. | ||||
| Ref 552910 | NF-kappaB: the inducible factors of HIV-1 transcription and their inhibitors. Mini Rev Med Chem. 2009 Jan;9(1):60-9. | ||||
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