Fachbereich Veterinärmedizin



    Does Clca1 Modulate the Innate Immune Response During DSS Challenge in the Murine Colon? (2015)

    Erickson, Nancy Ann (WE 12)
    Mundhenk, Lars (WE 12)
    Glauben, R.
    Giovannini, Samoa (WE 12)
    Nyström, E. E. L.
    Johansson, M. E. V.
    Gruber, Achim Dieter (WE 12)
    The 33rd Annual Meeting of The European Society of Veterinary Pathology & The 26th Annual Meeting of The European College of Veterinary Pathologists
    Fulda, Deutschland, 02. – 05.09.2015
    Journal of Comparative Pathology; 154(1) — S. 76
    ISSN: 0021-9975
    URL (Volltext): http://www.sciencedirect.com/science/article/pii/S0021997515001796
    DOI: 10.1016/j.jcpa.2015.10.044
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
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    Abstract / Zusammenfassung

    Introduction: Clca1, which is highly expressed in goblet cells, is thought to play a yet undefined role in early immune responses. It modulates the cytokine response and consecutive leucocyte recruitment in acute pneumonia and is found abundantly in the colonic mucus with an expression pattern similar to Muc2, the major structural mucus component. This study was designed to test whether Clca1 has an impact on the colonic immune response by modulating cytokine expression and/or as a structural mucus protein.

    Materials and Methods: Clca1-knockout (Clca1−/−) and wild type (WT) mice (n = 8–10) were analyzed under naïve conditions and at various time points following dextran sodium sulphate (DSS) challenge via disease activity index (DAI) and histopathology. Select cytokines were quantified at the mRNA and protein levels by RT-qPCR and cytometric bead array, respectively. Bacterial penetrability of the intestinal mucus barrier was characterized via anti-Muc2-immunofluorescence and 16S rRNA in-situ hybridization.

    Results: A more than two-fold increase of Cxcl-1 and Il-17 gene expression during DSS colitis and a five-times lower IFN-γ gene expression at earlier times were present in Clca1−/− compared with WT mice, with no further differences between the genotypes, irrespective of challenge.

    Conclusions: Despite Clca1 being a major constituent of the intestinal mucus barrier, it seems to have no impact on DSS-induced mucus barrier disruption and colitis. However, it appears to play a role in cytokine regulation depending on challenge type. The significance of differential IFN-γ gene expression is still unclear in light of lack of immune cell infiltration at these time points.