It is crucial to investigate the mechanism in how exactly IL-17Ra signaling is affecting the differentiation of intestinal epithelial cells. To do this, Pdgfra mediated secretion of factors such as Wnt ligand and r-spondins need to be analyzed. These factors are required for intestinal epithelial cell differentiation, and need to be quantified in the wild-type and IL-17Ra knockout mice in order to see if the IL-17Ra signaling pathway is affected. Since tuft cells are involved in sensing parasites, immune modulation and overall play a positive role in the immune system, the downregulation may lead to susceptibility to various diseases and an increased likelihood of inflammation. The loss of tuft cells may disrupt the intestinal epithelium’s role, and the barrier’s ability to regulate immune function, and thus negative gastrointestinal symptoms in humans. This is why the tuft cell function should be tested.

While histological analysis, alcian blue staining, but not qPCR analysis showed an increased number of goblet cells it may be crucial to analyze the function of the goblet cells. Since Muc2, the qPCR marker used, is an indicator of mucin production which is a marker for goblet cells, it may be possible that mucin production is altered. It is important to then analyze goblet cell function, or another qPCR marker of goblet cells, in order to confirm the last qPCR results.

Histological analysis, hematoxylin and eosin staining, showed an increased length of the crypt villi in IL-17Ra knockout mice. This suggests that IL-17Ra is affecting the differentiation, proliferation or migration of specialized cells in the intestinal epithelium. This elongation may be a compensatory mechanism in order to maintain barrier function. Thus, other factors previously mentioned such as gut microbiota quantification, and the quantification of Pdgfra mediated secretion of factors must be analyzed.

References

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• Mosca, M., Hong, J., Hadeler, E., Hakimi, M., Liao, W., & Bhutani, T. (2021). The Role of IL-17 Cytokines in Psoriasis. ImmunoTargets and Therapy, Volume 10, 409–418. https://doi.org/10.2147/itt.s240891
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