| First Author | Gonzalez-Quintial R | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 11 | Pages | e27528 |
| PubMed ID | 22102903 | Mgi Jnum | J:180964 |
| Mgi Id | MGI:5308481 | Doi | 10.1371/journal.pone.0027528 |
| Citation | Gonzalez-Quintial R, et al. (2011) Systemic autoimmunity and lymphoproliferation are associated with excess IL-7 and inhibited by IL-7Ralpha blockade. PLoS One 6(11):e27528 |
| abstractText | Lupus is characterized by disturbances in lymphocyte homeostasis, as demonstrated by the marked accumulation of activated/memory T cells. Here, we provide evidence that proliferation of the CD8+ precursors for the accumulating CD4CD8 T cells in MRL-Fas(lpr) lupus-predisposed mice is, in part, driven by commensal antigens. The ensuing lymphadenopathy is associated with increased production of IL-7 due to expansion of fibroblastic reticular cells, the primary source of this cytokine. The excess IL-7 is not, however, consumed by CD4CD8 T cells due to permanent down-regulation of IL-7Ralpha (CD127), but instead supports proliferation of autoreactive T cells and progression of autoimmunity. Accordingly, IL-7R blockade reduced T cell activation and autoimmune manifestations even when applied at advanced disease stage. These findings indicate that an imbalance favoring production over consumption of IL-7 may contribute to systemic autoimmunity, and correction of this imbalance may be a novel therapeutic approach in lymphoproliferative and autoimmune syndromes. |
