IL-7 stimulates the differentiation of multipotent (pluripotent) hematopoieticstem cells intolymphoid progenitor cells (as opposed to myeloid progenitor cells where differentiation is stimulated byIL-3).[citation needed] It also stimulates proliferation of all cells in the lymphoid lineage (B cells,T cells andNK cells).[citation needed] It is important for proliferation during certain stages of B-cell maturation, T and NK cell survival, development andhomeostasis.[citation needed]
IL-7 is acytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form aheterodimer that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRß) during early T cell development.[16] This cytokine can be produced locally by intestinal epithelial and epithelialgoblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes.[citation needed]Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.[17]
IL-7 receptor and signaling, common γ chain (blue) and IL-7 receptor-α (green)
IL-7 binds to theIL-7 receptor, a heterodimer consisting ofInterleukin-7 receptor alpha andcommon gamma chain receptor.[18] Binding results in a cascade of signals important for T-cell development within the thymus and survival within the periphery. Knockout mice which genetically lack IL-7 receptor exhibit thymicatrophy, arrest of T-cell development at the double positive stage, and severelymphopenia. Administration of IL-7 to mice results in an increase in recent thymic emigrants, increases in B and T cells, and increased recovery of T cells aftercyclophosphamide administration or after bone marrow transplantation.
IL-7 as animmunotherapy agent has been examined in many pre-clinical animal studies and more recently in human clinical trials for various malignancies and duringHIV infection.[13][21]
Recombinant IL-7 has been safely administered to patients in several phase I and IIclinical trials. A human study of IL-7 in patients withcancer demonstrated that administration of this cytokine can transiently disrupt the homeostasis of both CD8+ and CD4+ T cells with a commensurate decrease in the percentage of CD4+CD25+Foxp3+ T regulatory cells.[22] No objective cancer regression was observed, however adose limiting toxicity (DLT) was not reached in this study due to the development of neutralizingantibodies against therecombinant cytokine.
Associated with antiretroviral therapy, IL-7 administration decreased local and systemic inflammations in patients that had incomplete T-cell reconstitution. These results suggest that IL-7 therapy can possibly improve the quality of life of those patients.[23]
^Sutherland GR, Baker E, Fernandez KE, Callen DF, Goodwin RG, Lupton S, Namen AE, Shannon MF, Vadas MA (July 1989). "The gene for human interleukin 7 (IL7) is at 8q12-13".Hum. Genet.82 (4):371–2.doi:10.1007/BF00274000.PMID2786840.S2CID30870920.
^Kröncke R, Loppnow H, Flad HD, Gerdes J (October 1996). "Human follicular dendritic cells and vascular cells produce interleukin-7: a potential role for interleukin-7 in the germinal center reaction".Eur. J. Immunol.26 (10):2541–4.doi:10.1002/eji.1830261040.PMID8898972.S2CID20992591.
^Or R, Abdul-Hai A, Ben-Yehuda A (December 1998). "Reviewing the potential utility of interleukin-7 as a promoter of thymopoiesis and immune recovery".Cytokines Cell. Mol. Ther.4 (4):287–94.PMID10068062.
^Napolitano LA, Grant RM, Deeks SG, et al. (January 2001). "Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis".Nat. Med.7 (1):73–9.doi:10.1038/83381.PMID11135619.S2CID22536639.
Appasamy PM (1999). "Biological and clinical implications of interleukin-7 and lymphopoiesis".Cytokines Cell. Mol. Ther.5 (1):25–39.PMID10390077.
Al-Rawi MA, Mansel RE, Jiang WG (2004). "Interleukin-7 (IL-7) and IL-7 receptor (IL-7R) signalling complex in human solid tumours".Histol. Histopathol.18 (3):911–23.PMID12792903.
Sica D, Rayman P, Stanley J, et al. (1993). "Interleukin 7 enhances the proliferation and effector function of tumor-infiltrating lymphocytes from renal-cell carcinoma".Int. J. Cancer.53 (6):941–7.doi:10.1002/ijc.2910530613.PMID8473051.S2CID41223517.
