In previous experiments

In previous experiments kinase assay we have analyzed the colon of IL-7GCDL mice after crossing them to reporter mice expressing eGFP only after the Cre-mediated deletion of a DNA stop cassette [20]. Since the IL-7GCDL mouse expresses Cre (but not eGFP) under control of the il-7 promoter, this approach enabled us to visualize IL-7 producing IEC and their progeny based on eGFP expression. In the colon of such F1 animals, entire crypts were eGFP positive [20] suggesting that the il-7 promoter is active in epithelial stem cells. This interpretation is supported by our current findings shown in Figure 1E and S1. Here, IL-7 expression is most prominent at the crypt base where stem cells are located [24]. Hence, colonic epithelial stem cells are a putative source of IL-7.

However, it remains to be shown which other IEC subtypes express IL-7 and its receptor to elucidate whether IL-7 regulates IEC homeostasis in lymphopenic mice in an autocrine and/or paracrine fashion. We have shown previously that the commensal microflora promotes il-7 gene expression in the intestine [20]. Consequently, intestinal BL and corresponding IL-7 levels in the colon (data not shown) were strongly reduced in antibiotic-treated Rag?IL-7GCDL mice (Figure S8A). This was associated with reduced colon wall thickness (Figure S8B) and lower levels of IEC proliferation (Figure S8C). Similar results were obtained with germ-free Rag? mice (Figure S8B and C) showing that the commensal microflora promotes IEC hyperplasia in Rag? mice, probably via the induction of il-7 gene expression [20].

It is known that the bacterial content of the large intestine is higher than in the small intestine. This may explain why il-7 gene activity is comparably low in the latter (Figure 1B) and why IEC homeostasis in this part of the gut is less severely affected by IL-7 (Figure S2). However, IL-7-dependent hyperplasia of the colonic epithelium correlates with changes in colon function (Figure 2D�CF) and alterations in the commensal microflora (Information S1 and Figure S8). IL-7 levels are elevated in HIV patients [4], which frequently suffer from diarrhea [33]. Cilengitide Similarly, severe combined immunodeficiency (SCID) patients often develop intestinal complications [34]. Due the broad impact of IL-7 on intestinal physiology shown here, it is tempting to speculate that the lymphopenia-associated overabundance of IL-7 promotes intestinal alterations frequently observed in lymphopenic patients. The nuclear translocation of ��-catenin is crucial for the maintenance of IEC homeostasis [24]. In a healthy colon, nuclear ��-catenin is mainly restricted to IEC located at the crypt base [24]. However, in the colon of Rag? mice, nuclear ��-catenin was also found in luminal IEC (Figure 5D).

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>