Transcriptomics

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The role of immunoglobulin A


ABSTRACT: Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium, and the microbiota. We found that mice lacking B lymphocytes, or lacking IgA, have low intestinal expression of lipid metabolism genes regulated by the transcription factor GATA4, and a consequent decrease in fat absorption in the intestine. The defect disappeared in germ free mice, suggesting that it is dependent on the microbiota; and sequencing analysis of the bacteria showed subtle differences between normal and B-cell deficient mice. Analysis of gene expression of gut biopsies from patients with common variable immunodeficiency and intestinal dysfunction revealed a high similarity to mouse B-cell knockout profiles. These data provide an explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans. This series represents the subsection of the study where we adress the role of immunoglobulin A. The data is from IgA KO and corresponding control mice. Intensity of each channel was extracted from two-color arrays. We used direct dye swap design and performed paired analysis between small intestine of KO and control mice. Corresponding paires of KO and control were hybridized on the same array and can be matched by the array name.

ORGANISM(S): Mus musculus  

SUBMITTER: Andrey Morgun   Natalia Shulzhenko 

PROVIDER: E-GEOD-33884 | ArrayExpress | 2011-11-23

SECONDARY ACCESSION(S): GSE33884PRJNA148315

REPOSITORIES: GEO, ArrayExpress

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Publications

Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut.

Shulzhenko Natalia N   Morgun Andrey A   Hsiao William W   Battle Michele M   Yao Michael M   Gavrilova Oksana O   Orandle Marlene M   Mayer Lloyd L   Macpherson Andrew J AJ   McCoy Kathy D KD   Fraser-Liggett Claire C   Matzinger Polly P  

Nature medicine 20111120 12


Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorpt  ...[more]

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