Soluble IL-7Rα/sCD127 in Health, Disease, and Its Potential Role as a Therapeutic Agent

Abstract

Soluble cytokine receptors can influence immune responses by modulating the biological functions of their respective ligands. These effects can be either agonistic or antagonistic and a number of soluble cytokine receptors have been shown to play critical roles in both maintenance of health and disease pathogenesis. Soluble IL-7Ra (sCD127) is one such example. With its impact on the IL-7/CD127 pathway, which is fundamental for the development and homeostasis of T cells, the role of sCD127 in health and disease has been extensively studied in recent years. Within this review, the role of sCD127 in maintaining host immune function is presented. Next, by addressing genetic factors affecting sCD127 expression and the associated levels of sCD127 production, the roles of sCD127 in autoimmune disease, infections and cancer are described. Finally, advances in the field of soluble cytokine therapy and the potential for sCD127 as a biomarker and therapeutic agent are discussed.

Keywords: IL-7; IL7RA; rs6897932 SNP; sCD127; sIL-7Rα; soluble cytokine receptor.

Figure 1

Possible mechanisms through which sCD127 influences IL-7-induced effects on CD8+ T cells. Most evidence suggest sCD127 has an agonistic effect on IL-7-induced activity on CD8+ T cells. sCD127 was shown to influence IL-7-induced effect through: (1) competition with mCD127 for binding to IL-7 molecules; (2) while engaged to IL-7, inducing lower consumption of the cytokine, thus, increasing its bioactivity, (3) inhibition of the activity of negative regulators of IL-7/CD127 pathway (eg, SOCS, CD95), and (4) amplification of IL-7-induced CD8+ T cell proliferation and viability.