Systemic Autoimmunity and Lymphoproliferation Are Associated with Excess IL-7 and Inhibited by IL-7R alpha Blockade

作者：Gonzalez Quintial Rosana^*; Lawson Brian R; Scatizzi John C; Craft Joseph; Kono Dwight H; Baccala Roberto; Theofilopoulos Argyrios N

来源：PLos One, 2011, 6(11): e27528.

DOI：10.1371/journal.pone.0027528

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 CD4(-)CD8(-) 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 CD4(-)CD8(-) T cells due to permanent down-regulation of IL-7R alpha (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.

• 出版日期2011-11-10