Seeing is believing: illuminating the source of in vivo interleukin-7

Abstract

Interleukin-7 (IL-7) is an essential cytokine for T cells. However, IL-7 is not produced by T cells themselves such that T cells are dependent on extrinsic IL-7. In fact, in the absence of IL-7, T cell development in the thymus as well as survival of naive T cells in the periphery is severely impaired. Furthermore, modulating IL-7 availability in vivo either by genetic means or other experimental approaches determines the size, composition and function of the T cell pool. Consequently, understanding IL-7 expression is critical for understanding T cell immunity. Until most recently, however, the spatiotemporal expression of in vivo IL-7 has remained obscured. Shortage of such information was partly due to scarce expression of IL-7 itself but mainly due to the lack of adequate reagents to monitor IL-7 expression in vivo. This situation dramatically changed with a recent rush of four independent studies that describe the generation and characterization of IL-7 reporter mice, all utilizing bacterial artificial chromosome transgene technology. The emerging consensus of these studies confirmed thymic stromal cells as the major producers of IL-7 but also identified IL-7 reporter activities in various peripheral tissues including skin, intestine and lymph nodes. Strikingly, developmental and environmental cues actively modulated IL-7 reporter activities in vivo suggesting that IL-7 regulation might be a new mechanism of shaping T cell development and homeostasis. Collectively, the availability of these new tools opens up new venues to assess unanswered questions in IL-7 biology in T cells and beyond.

Keywords: Bacterial artificial chromosome; Homeostasis; T cells; Thymus.

Figure 1

Schematic representation of the BAC constructs for IL-7 reporter mice. Endogenous wildtype IL-7 locus is shown at the top. Alves et al. (51) generated BAC transgenic mice encoding the yellow fluorescent protein (YFP) under the control of the IL-7 promoter. The YFP gene was inserted by homologous recombination downstream of the ATG transcriptional start codon of exon 1 of the IL-7 locus. Repass et al. (52) generated two BAC transgenic mice where IL-7 regulatory elements drive either Cre recombinase (IL-7.Cre) or human CD25 (IL-7.hCD25) reporter expression. Mazzucchelli et al. (53) generated BAC transgenic mice encoding the enhanced cyan fluorescence protein (ECFP) under the control of the IL-7 promoter (IL7promECFP). The exon 1 sequence, encoding the signal peptide was replaced with the Ecfp cDNA sequence starting after the ATG start site. Shalapour et al. (54) generated BAC transgenic mice simultaneously expressing enhanced green fluorescent protein (G), recombinase Cre (C), the human diphtheria toxin receptor (D) and click beetle green luciferase 99 (L) under control of the IL-7 promoter (IL-7GCDL). E1~E5: Exon 1~Exon 5. UTR: Untranslated region.