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Immunology

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Description

Interleukin-7 (IL-7) was initially isolated more than 10 years ago. Nevertheless, the complete set of physiologic roles for this cytokine, especially those involving lymphocyte homeostasis, have only recently been elucidated. After the initial descriptions of effects on B-cell precursors, recognition that IL-7 also has marked activity on immature and mature T cells soon followed. Information from gene-deleted mice showed IL-7 is a nonredundant cytokine for murine T and B lymphopoiesis.

Mutations in the alpha chain of the IL-7 receptor in patients with severe combined immunodeficiency (SCID) confirmed that IL-7 is indispensable for T-cell development in humans. However, the presence of B cells in these individuals suggests important differences between the role of IL-7 in murine and human lymphocyte development.

IL-7 also has potent effects on mature T cells. Recent work has shown that IL-7 is a critical modulator of low-affinity peptide-induced proliferation, which is a central feature of the homeostatic regulation of T-cell populations. Furthermore, circulating levels of IL-7 increase in response to T-cell depletion, suggesting a role in T-cell regeneration.Importantly, the primary sources of IL-7 are non-marrow-derived stromal and epithelial cells. Thus, IL-7 is a pleiotropic cytokine with central roles in modulating T- and B-cell development and T-cell homeostasis. The potency and breadth of effects suggest that IL-7 administration or neutralization of IL-7 may allow the modulation of immune function in patients with lymphocyte depletion, vaccine administration, or autoimmunity. (1)

Discussion

IL7R is involved in inflammation and immune response. Though a role in human ageing has not been demonstrated, it is possible that IL7R is related to age-related changes and pathologies, namely, at the level of the immune system

Although IL7 could play a role age-related changes, such as aging of the immune system, its role in human aging is unknown.

Interleukin-7 (IL7) stimulates the proliferation of lymphoid progenitors. Mice without IL7 cease producing B lymphocyte after 7 weeks of age. Interleukin-7 is needed for both generation of T lymphocytes in the thymus as well as maintenance of mature T lymphocytes. Declines with age in IL7 production have been associated with thymic atrophy. (2)

This theme of improved immunity following reversal of thymic atrophy was carried further in work reported by Dr Richard Aspinall (Imperial College, London). He showed how therapeutic intervention with interleukin 7 and derivates could reverse atrophy of the thymus in old animals and also lead to improved immune function compared with age and sex matched controls. In addition he described work done in the Gambia which suggested a link between the development and enlargement of the thymus after birth and the level of interleukin 7 in breast milk. (3)

The human DF3/MUC1 transmembrane protein is aberrantly expressed in multiple myeloma cells and other B cell malignancies. The regulation of MUC1 in B cells and its potential function as a signaling molecule are unknown. Results demonstrate that interleukin-7 (IL-7) stimulates MUC1 expression in multiple myeloma cells. (4)

Links

References


1. Terry J. Fry and Crystal L. Mackall.Interleukin-7: from bench to clinic. Blood, 1 June 2002, Vol. 99, No. 11, pp. 3892-3904

2. Andrew D, Aspinall R. Age-associated thymic atrophy is linked to a decline in IL-7 production. Exp Gerontol. 2002 Jan-Mar;37 (2-3):455-63.

3. Aspinal R: Age-related changes in the function of T cells. Microsc Res Tech 2003, 62:508-513.

4. Li Y, Chen W, Ren J, Yu WH, Li Q, Yoshida K, Kufe D. DF3/MUC1 signaling in multiple myeloma cells is regulated by interleukin-7. Cancer Biol Ther. 2003 Mar-Apr;2(2):194-5.

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