Abstract
IL-7 is an essential, nonredundant growth factor for T and B cell generation and maintenance. While IL-7 deficiency results in lymphopenia, overexpression of IL-7 can cause neoplasia in experimental models. IL-7’s involvement in neoplasia has been appreciated through studies of IL-7 transgenic (Tg) mice models and human lymphoma patients. Since we recently found that a soluble form of the common γ-chain (γc) cytokine receptor (sγc) antagonistically regulates IL-7 signaling, IL-7 and sγc double-Tg mice were generated to investigate the effects of sγc overexpression in IL-7-mediated lymphoproliferative disorders (LPDs). The overexpression of sγc prevents IL-7Tg-induced abnormal increase of LN cell numbers and the development of splenomegaly, resulting in striking amelioration of mortality and disease development. These results suggest that modification of γc cytokine responsiveness by sγc molecules might control various γc cytokine-associated hematologic malignancy, and also provide an alternative view to approach antitumor therapy.
Highlights
IL-7 is one of the γc cytokines that are a major factor in T-cell development and differentiation [1]
IL-7 exerts its effect through interaction with the IL-7 receptor (IL-7R), which is composed of a unique α chain (IL-7Rα) and γc, whereby expression of IL-7Rα mainly determines the timing and extent of IL-7 signaling [1,4], since γc expression is presumed to remain unchanged on lymphocytes
We demonstrated that sγc regulates γc cytokine signaling with the generation of sγc-overexpressing transgenic mice [13,14,16]
Summary
IL-7 is one of the γc cytokines that are a major factor in T-cell development and differentiation [1]. IL-7 exerts its effect through interaction with the IL-7 receptor (IL-7R), which is composed of a unique α chain (IL-7Rα) and γc, whereby expression of IL-7Rα mainly determines the timing and extent of IL-7 signaling [1,4], since γc expression is presumed to remain unchanged on lymphocytes. This was proven by IL-7Tg animal models that were heterozygous with the IL-7Rα subunit and improved survival compared to wild-type (WT) IL-7Tg mice [5,6]. We suggest that the therapeutic potential of sγc could be applied and expanded to immune-associated diseases like autoimmune disease and infection
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