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  1. Article ; Online: The interplay between bile acids and mucosal adaptive immunity.

    Mohammed, Ahmed Dawood / Ball, Ryan A W / Kubinak, Jason L

    PLoS pathogens

    2023  Volume 19, Issue 6, Page(s) e1011356

    MeSH term(s) Bile Acids and Salts ; Mucous Membrane ; Adaptive Immunity ; Immunity, Mucosal
    Chemical Substances Bile Acids and Salts
    Language English
    Publishing date 2023-06-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011356
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Studying the cellular basis of small bowel enteropathy using high-parameter flow cytometry in mouse models of primary antibody deficiency.

    Mohammed, Ahmed D / Ball, Ryan A W / Jolly, Amy / Nagarkatti, Prakash / Nagarkatti, Mitzi / Kubinak, Jason L

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Background: Primary immunodeficiencies are heritable defects in immune system function. Antibody deficiency is the most common form of primary immunodeficiency in humans, can be caused by abnormalities in both the development and activation of B cells, ... ...

    Abstract Background: Primary immunodeficiencies are heritable defects in immune system function. Antibody deficiency is the most common form of primary immunodeficiency in humans, can be caused by abnormalities in both the development and activation of B cells, and may result from B-cell-intrinsic defects or defective responses by other cells relevant to humoral immunity. Inflammatory gastrointestinal complications are commonly observed in antibody-deficient patients, but the underlying immune mechanisms driving this are largely undefined.
    Methods: In this study, several mouse strains reflecting a spectrum of primary antibody deficiency (IgA
    Results: Results from our experiments indicate that the severity of primary antibody deficiency positively correlates with the degree of immune dysregulation that can be expected to develop in an individual. In the SI of mice, immune dysregulation is primarily explained by defective homeostatic responses in T cell and invariant natural killer-like T (iNKT) cell subsets. These defects are strongly correlated with abnormalities in the balance between protein (MHCII-mediated) versus lipid (CD1d-mediated) antigen presentation by intestinal epithelial cells (IECs) and intestinal stem cells (ISCs), respectively.
    Conclusions: Multivariate statistical approaches can be used to obtain quantifiable estimates of immune dysregulation based on high-parameter flow cytometry readouts of immune function. Using one such estimate, we reveal a previously unrecognized tradeoff between iNKT cell activation and type 1 immunity that underlies disease in the small bowel. The balance between protein/lipid antigen presentation by ISCs may play a crucial role in regulating this balance and thereby suppressing inflammatory disease in the small bowel.
    Language English
    Publishing date 2024-01-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.25.577009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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