| First Author | Lee SK | Year | 2012 |
| Journal | Immunity | Volume | 37 |
| Issue | 5 | Pages | 880-92 |
| PubMed ID | 23159227 | Mgi Jnum | J:190440 |
| Mgi Id | MGI:5448869 | Doi | 10.1016/j.immuni.2012.10.010 |
| Citation | Lee SK, et al. (2012) Interferon-gamma excess leads to pathogenic accumulation of follicular helper T cells and germinal centers. Immunity 37(5):880-92 |
| abstractText | Overactivity of the germinal center (GC) pathway resulting from accumulation of follicular helper T (Tfh) cells causes autoimmunity, underscoring the need to understand the factors that control Tfh cell homeostasis. Here we have identifed posttranscriptional repression of interferon-gamma (Ifng) mRNA as a mechanism to limit Tfh cell formation. By using the sanroque lupus model, we have shown that decreased Ifng mRNA decay caused excessive IFN-gamma signaling in T cells and led to accumulation of Tfh cells, spontaneous GC, autoantibody formation, and nephritis. Unlike ICOS and T-bet deficiency that failed to rescue several autoimmune manifestations, interferon-gamma receptor (IFN-gammaR) deficiency prevented lupus development. IFN-gamma blockade reduced Tfh cells and autoantibodies, demonstrating that IFN-gamma overproduction was required to sustain lupus-associated pathology. Increased IFN-gammaR signaling caused Bcl-6 overexpression in Tfh cells and their precursors. This link between IFN-gamma and aberrant Tfh cell formation provides a rationale for IFN-gamma blockade in lupus patients with an overactive Tfh cell-associated pathway. |
