Interleukin 7

Interleukin 7 (IL-7) is a is_associated_with::protein that in humans is encoded by the IL7 is_associated_with::gene.

IL-7 a hematopoietic is_associated_with::growth factor secreted by is_associated_with::stromal cells in the is_associated_with::bone marrow and is_associated_with::thymus. It is also produced by is_associated_with::keratinocytes, is_associated_with::dendritic cells, is_associated_with::hepatocytes, is_associated_with::neurons, and is_associated_with::epithelial cells but is not produced by normal is_associated_with::lymphocytes.

Structure
The three-dimensional structure of IL-7 in complex with the is_associated_with::ectodomain of is_associated_with::IL7R has been determined using X-ray diffraction.

T cell maturation
IL-7 stimulates the differentiation of multipotent (pluripotent) hematopoietic is_associated_with::stem cells into is_associated_with::lymphoid progenitor cells (as opposed to myeloid progenitor cells where differentiation is stimulated by IL-3). It also stimulates proliferation of all cells in the lymphoid lineage (is_associated_with::B cells, is_associated_with::T cells and NK cells). It is important for proliferation during certain stages of B-cell maturation, T and NK cell survival, development and is_associated_with::homeostasis.

IL-7 is a is_associated_with::cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a is_associated_with::heterodimer 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. This cytokine can be produced locally by intestinal epithelial and epithelial is_associated_with::goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. is_associated_with::Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.

IL-7 signaling


IL-7 binds to the IL-7 receptor, a heterodimer consisting of Interleukin-7 receptor alpha and common gamma chain receptor. 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 thymic is_associated_with::atrophy, arrest of T-cell development at the double positive stage, and severe is_associated_with::lymphopenia. 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 after is_associated_with::cyclophosphamide administration or after bone marrow transplantation.

Cancer
IL-7 promotes hematological malignancies (acute lymphoblastic leukemia, T cell lymphoma).

Viral Infections
Elevated levels of IL-7 have also been detected in the plasma of HIV-infected patients.

Clinical application
IL-7 as an is_associated_with::immunotherapy agent has been examined in many pre-clinical animal studies and more recently in human clinical trials for various malignancies and during HIV infection.

Cancer
Recombinant IL-7 has been safely administered to patients in several phase I and II is_associated_with::clinical trials. A human study of IL-7 in patients with is_associated_with::cancer 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. No objective cancer regression was observed, however a is_associated_with::dose limiting toxicity (DLT) was not reached in this study due to the development of neutralizing is_associated_with::antibodies against the is_associated_with::recombinant cytokine.

HIV infection
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.

Transplantation
IL-7 could also be beneficial in improving immune recovery after allogenic stem cell transplant.