Inflammatory bowel diseases

Oral

Human Resident Intestinal Lamina Propria Cells Rapidly Upregulate Protein Translation and Mtor Pathway Activity During the Induction of an Inflammatory Response

Wednesday, June 14
6:15 PM - 7:45 PM

Under steady-state conditions, human resident intestinal lamina propria (LP) leukocytes (LPL) exhibit low reactivity to bacterial/nutritional antigens as present in the gut lumen and thereby contribute to local immune homeostasis. Under adverse conditions, however, LPL rapidly acquire an activated phenotype characterized by the expression of inflammation-associated genes, and hence actively participate in the regulation of intestinal inflammation. Molecular mechanisms driving the switch from a hyporesponsive to an inflammatory state in LPL are currently unkown.


Here, we addressed the regulation of protein translation during the induction of an inflammatory response in LP cells. For this purpose, we employed a human intestinal organ culture model, in which an inflammatory response is elicited in LP cells upon loss of the epithelial layer (LEL model). Using OPP Click-It technology, we observed that –in comparison to epithelial cells or peripheral blood immune cells- global protein synthesis was low in LP cells under homeostatic conditions and was rapidly upregulated during onset of inflammation, particularly in IgA+plasma cells and CD68+macrophages. Upregulation of protein translation in macrophages but not plasma cells was partially dependent on mTOR activation. In line with this observation, mTOR activation contributed to the inflammation-associated secretion of the chemokines CCL2/CCL19/CCL22/CXCL1, which are known to be produced by macrophages.


In summary, upregulation of global protein translation and mTOR pathway activity represent early events during the initiation of an inflammatory response in human resident LPL. By mediating chemokine secretion in LP cells they may contribute to the recruitment of immune cells to inflamed mucosal sites.

Jutta Schroeder-Braunstein

Institute of Immunology, University Hospital Heidelberg

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    Judith Gras

    Institute of Immunology, University Hospital Heidelberg

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      Felix Lasitschka

      Institute of Pathology, University Hospital Heidelberg

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        Guido Wabnitz

        Institute of Immunology, University Hospital Heidelberg

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          Niels Halama

          National Center for Tumor Diseases Heidelberg, University Hospital Heidelberg

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            Antje Heidtmann

            Institute of Immunology, University Hospital Heidelberg

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              Sabine Wentrup

              Institute of Immunology, University Hospital Heidelberg

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                Mohammed Al-Saeedi

                Department of Surgery, University Hospital Heidelberg

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                  Thomas Giese

                  Institute of Immunology, University Hospital Heidelberg

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                    Stefan Meuer

                    Institute of Immunology, University Hospital Heidelberg

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