| First Author | Tang W | Year | 2021 |
| Journal | Eur J Immunol | Volume | 51 |
| Issue | 1 | Pages | 197-205 |
| PubMed ID | 32652549 | Mgi Jnum | J:302238 |
| Mgi Id | MGI:6507795 | Doi | 10.1002/eji.202048584 |
| Citation | Tang W, et al. (2021) Bcl-3 inhibits lupus-like phenotypes in BL6/lpr mice. Eur J Immunol 51(1):197-205 |
| abstractText | Bcl-3 is an atypical member of the IkappaB family that modulates NF-kappaB activity in nuclei. lpr mice carry the lpr mutation in Fas, resulting in functional loss of this death receptor; they serve as models for lupus erythematosus and autoimmune lymphoproliferation syndrome (ALPS). To explore the biologic roles of Bcl-3 in this disease model, we generated BL6/lpr mice lacking Bcl-3. Unlike lpr mice on an MRL background, BL6/lpr mice present with very mild lupus- or ALPS-like phenotypes. Bcl-3 KO BL6/lpr mice, however, developed severe splenomegaly, dramatically increased numbers of double negative T cells - a hallmark of human lupus, ALPS, and MRL/lpr mice - and exhibited inflammation in multiple organs, despite low levels of autoantibodies, similar to those in BL6/lpr mice. Loss of Bcl-3 specifically in T cells exacerbated select lupus-like phenotypes, specifically organ infiltration. Mechanistically, elevated levels of Tnfalpha in Bcl-3 KO BL6/lpr mice may promote lupus-like phenotypes, since loss of Tnfalpha in these mice reversed the pathology due to loss of Bcl-3. Contrary to the inhibitory functions of Bcl-3 revealed here, this regulator has also been shown to promote inflammation in different settings. Our findings highlight the profound, yet highly context-dependent roles of Bcl-3 in the development of inflammation-associated pathology. |
