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Innate defense responses in Muc2 deficient mice: an important role for goblet cells
Author(s) -
Burgervan Paassen Nanda,
Bouma Janneke,
Bruijn Adrianus CJM,
Sluis Maria,
Van Seuningen Isabelle,
Van Goudoever Johannes B,
Renes Ingrid B
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.121.2
Subject(s) - downregulation and upregulation , mucus , inflammation , knockout mouse , biology , microbiology and biotechnology , innate immune system , immunology , andrology , gene , medicine , biochemistry , immune system , ecology
Background Absence of a mucus layer, as in Muc2 knockout (KO) mice, leads the induction of colitis due to aberrant bacterial‐epithelial interactions. We hypothesize that innate defense molecules, i.e. bactericidal peptides, are upregulated in Muc2KO mice to compensate for loss of the mucus layer. Aim To study the innate defense response in Muc2KO mice. Methods Colonic tissue of Muc2KO and wild type (WT) mice was collected up to 28 days after birth. Expression of the bactericidal peptides; regenerating gene (Reg)3β, Reg3γ and angiogenin (Ang)4 was studied by qPCR, in situ hybridization and/or immunohistochemistry. Additionally, influx of T cells into the mucosa was studied as marker for inflammation. Results Compared to WT mice, Reg3β and Reg3γ mRNA levels were increased up to 50 fold in KO mice at 14 days, and a further increase was seen at 28 days. In contrast, Ang4 expression was observed in the colon of WT mice, but not in the colon of KO mice. Finally, the number of infiltrating T cells in the colon increased with age in KO mice. Conclusions Strong upregulation of Reg3β and Reg3γ in the colon of KO mice suggests increased innate defense capacity to compensate for the loss of intestinal barrier function. Reg3 gene expression correlates with the increased influx of T‐cells, implying a role for Reg3 peptides in intestinal inflammation. Absence of Ang4 expression in KO mice might indicate diminished bactericidal activity.