Interleukin-7 (IL-7) is a 25 kDa cytokine of the hemopoietin family that plays important roles in lymphocyte differentiation, proliferation, and survival [1-4]. Mouse IL-7 cDNA encodes 154 amino acids (aa) that include a 25 aa signal peptide [4]. Mouse IL-7 shares approximately 88% aa sequence identity with rat IL-7 and 58-60% with human, equine, bovine, ovine, porcine, feline and canine IL-7. Human and mouse IL-7 exhibit cross-species activity [2, 3]. IL-7 is produced by a wide variety of cells in primary and secondary lymphoid tissues, including stromal epithelial cells of the thymus, bone marrow, and intestines [1, 2, 5]. Circulating IL-7 is limiting in healthy animals, but increases during lymphopenia [1, 6]. IL-7 signals through a complex of the IL-7 Receptor alpha subunit (IL-7 R alpha, also known as CD127) with the common gamma chain ( gamma c) [1]. The gamma c is also a subunit of the receptors for IL-2, -4, -9, -15, and -21 [1]. IL-7 R alpha is expressed on double negative (CD4-CD8-) and CD4+ or CD8+ single positive memory T cells, but undergoes IL-7-mediated down-regulation and shedding during antigen-driven T cell proliferation, and is absent on regulatory T cells [1, 2, 6-11]. IL-7 contributes to the maintenance of all memory T cells, mainly by promoting expression of the anti-apoptotic protein Bcl-2 [9-11]. It is required for optimal T cell-dendritic cell interaction [6]. IL-7 is expressed early in B cell development prior to the appearance of surface IgM [1, 5, 9]. In mouse, IL-7 activation of IL-7 R alpha is critical for both T cell and B cell lineage development, while in humans, it is required for T cell but not for B cell development [4, 9, 12, 13].
Reference
[1]. Sasson, S.C. et al. (2006) Curr. Drug Targets 7:1571.
[2]. Barata, J.T. et al. (2006) Exp. Hematol. 34:1133.
[3]. Goodwin, R.G. et al. (1990) Proc. Natl. Acad. Sci. USA 86:302.
[4]. Namen, A.E. et al. (1988) Nature 333:571.
[5]. Shalapour, S. et al. (2012) PLoS ONE 7: e31939.
[6]. Saini, M. et al. (2009) Blood 113:5793.
[7]. Park, J.H. et al. (2004) Immunity 21:289.
[8]. Vranjkovic, A. et al. (2007) Int. Immunol. 19:1329.
[9]. Sudo, T. et al. (1993) Proc. Natl. Acad. Sci. 90:9125.
[10]. Seddon, B. et al. (2003) Nat. Immunol. 4:680.
[11]. Schluns, K.S. et al. (2000) Nat. Immunol. 5:426.
[12]. Peschon, J.J. et al. (1994) J. Exp. Med. 180:1955.
[13]. Pribyl, J.A. and T.W. LeBien (1996) Proc. Natl. Acad. Sci. 93:10348.