Back to Search
Start Over
Immunoglobulin A-specific deficiency induces spontaneous inflammation specifically in the ileum.
- Source :
-
Gut [Gut] 2022 Mar; Vol. 71 (3), pp. 487-496. Date of Electronic Publication: 2021 May 07. - Publication Year :
- 2022
-
Abstract
- Objective: Although immunoglobulin A (IgA) is abundantly expressed in the gut and known to be an important component of mucosal barriers against luminal pathogens, its precise function remains unclear. Therefore, we tried to elucidate the effect of IgA on gut homeostasis maintenance and its mechanism.<br />Design: We generated various IgA mutant mouse lines using the CRISPR/Cas9 genome editing system. Then, we evaluated the effect on the small intestinal homeostasis, pathology, intestinal microbiota, cytokine production, and immune cell activation using intravital imaging.<br />Results: We obtained two lines, with one that contained a <50 base pair deletion in the cytoplasmic region of the IgA allele (IgA tail-mutant; IgA <superscript>tm/tm</superscript> ) and the other that lacked the most constant region of the IgH α chain, which resulted in the deficiency of IgA production (IgA <superscript>-/-</superscript> ). IgA <superscript>-/-</superscript> exhibited spontaneous inflammation in the ileum but not the other parts of the gastrointestinal tract. Associated with this, there were significantly increased lamina propria CD4 <superscript>+</superscript> T cells, elevated productions of IFN-γ and IL-17, increased ileal segmented filamentous bacteria and skewed intestinal microflora composition. Intravital imaging using Ca <superscript>2+</superscript> biosensor showed that IgA <superscript>-/-</superscript> had elevated Ca <superscript>2+</superscript> signalling in Peyer's patch B cells. On the other hand, IgA <superscript>tm/tm</superscript> seemed to be normal, suggesting that the IgA cytoplasmic tail is dispensable for the prevention of the intestinal disorder.<br />Conclusion: IgA plays an important role in the mucosal homeostasis associated with the regulation of intestinal microbiota and protection against mucosal inflammation especially in the ileum.<br />Competing Interests: Competing interests: None declared.<br /> (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
- Subjects :
- Animals
B-Lymphocytes physiology
Cytokines metabolism
Disease Models, Animal
Female
Gastrointestinal Microbiome
Homeostasis
Ileitis metabolism
Ileitis pathology
Ileum metabolism
Ileum ultrastructure
Inflammation etiology
Inflammation metabolism
Inflammation pathology
Intravital Microscopy
Male
Mice
Mice, Mutant Strains
T-Lymphocytes physiology
Ileitis etiology
Ileum pathology
Immunoglobulin A physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1468-3288
- Volume :
- 71
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Gut
- Publication Type :
- Academic Journal
- Accession number :
- 33963042
- Full Text :
- https://doi.org/10.1136/gutjnl-2020-322873