IL-7 in human health and disease

IL-7 plays many essential roles in human health and disease. Congenital deficiencies in IL-7 signaling result in profound immunodeficiency, polymorphisms in IL7Rα modulate susceptibility to autoimmune disease, and acquired somatic activating mutations in IL7Rα contribute to neoplastic transformation in B cell and T cell leukemia. In response to lymphopenia, IL-7 accumulates to supranormal levels, which alters T cell homeostasis by augmenting T cell reactivity toward self and cognate antigens. This physiologic response is now routinely exploited to improve the efficacy of adoptive cell therapies for cancer. Clinical trials of recombinant IL-7 have demonstrated safety and potent immunorestorative effects, and current studies are investigating whether rhIL-7 therapy can improve outcomes in chronic viral infection and in the context of cancer immunotherapies. Building upon the large fund of knowledge regarding the basic biology of IL-7, this review will discuss the many and varied roles of IL-7 in human health and disease.

► In man, IL-7 is essential for T cell development, and contributes to B cell development.
► Human IL-7 is a major modulator of T-cell homeostasis.
► IL7R genotype influences susceptibility to several autoimmune diseases.
► Gain-of-function mutations in IL7R and CRLF2 contribute to oncogenesis in leukemia.
► Clinical trials using rhIL-7 show it to be well tolerated with promising activity.