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1.
Proc Natl Acad Sci U S A ; 119(3)2022 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-35027453

RESUMEN

Paneth cells are intestinal epithelial cells that release antimicrobial peptides, such as α-defensin as part of host defense. Together with mesenchymal cells, Paneth cells provide niche factors for epithelial stem cell homeostasis. Here, we report two subtypes of murine Paneth cells, differentiated by their production and utilization of fucosyltransferase 2 (Fut2), which regulates α(1,2)fucosylation to create cohabitation niches for commensal bacteria and prevent invasion of the intestine by pathogenic bacteria. The majority of Fut2- Paneth cells were localized in the duodenum, whereas the majority of Fut2+ Paneth cells were in the ileum. Fut2+ Paneth cells showed higher granularity and structural complexity than did Fut2- Paneth cells, suggesting that Fut2+ Paneth cells are involved in host defense. Signaling by the commensal bacteria, together with interleukin 22 (IL-22), induced the development of Fut2+ Paneth cells. IL-22 was found to affect the α-defensin secretion system via modulation of Fut2 expression, and IL-17a was found to increase the production of α-defensin in the intestinal tract. Thus, these intestinal cytokines regulate the development and function of Fut2+ Paneth cells as part of gut defense.


Asunto(s)
Citocinas/metabolismo , Fucosiltransferasas/metabolismo , Microbioma Gastrointestinal/fisiología , Células de Paneth/metabolismo , Animales , Fucosiltransferasas/genética , Íleon , Interleucina-17/metabolismo , Interleucinas/metabolismo , Ratones , Simbiosis , alfa-Defensinas/metabolismo , Interleucina-22 , Galactósido 2-alfa-L-Fucosiltransferasa
2.
Allergol Int ; 68(1): 17-25, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30366757

RESUMEN

Despite its direct exposure to huge amounts of microorganisms and foreign and dietary antigens, the gut mucosa maintains intestinal homeostasis by utilizing the mucosal immune system. The gut mucosal immune system protects the host from the invasion of infectious pathogens and eliminates harmful non-self antigens, but it allows the cohabitation of commensal bacteria in the gut and the entry of dietary non-self antigens into the body via the mucosal surface. These physiological and immunological activities are regulated by the ingenious gut mucosal immune network, comprising such features as gut-associated lymphoid tissue, mucosal immune cells, cytokines, chemokines, antimicrobial peptides, secretory IgA, and commensal bacteria. The gut mucosal immune network keeps a fine tuned balance between active immunity (against pathogens and harmful non-self antigens) and immune tolerance (to commensal microbiota and dietary antigens), thus maintaining intestinal healthy homeostasis. Disruption of gut homeostasis results in persistent or severe gastrointestinal infection, inflammatory bowel disease, or allergic inflammation. In this review, we comprehensively introduce current knowledge of the gut mucosal immune system, focusing on its interaction with allergic inflammation.


Asunto(s)
Tracto Gastrointestinal/inmunología , Hipersensibilidad/inmunología , Inmunidad Mucosa , Animales , Antígenos/inmunología , Dieta , Humanos , Tolerancia Inmunológica , Inmunoglobulina A/inmunología , Inflamación/inmunología
3.
Front Immunol ; 10: 1281, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31275305

RESUMEN

The epithelial layer creates a chemical and physical barrier at the forefront of intestinal mucosa, and immune cells beneath the surface epithelium are poised to react to extrinsic factors, to maintain tissue homeostasis. Importantly, the nexus of epithelial-immune responses at mucosal surfaces is dexterously modulated by intrinsic stromal-mesenchymal cells. First, organogenesis of lymphoid tissues, including Peyer's patches, requires dynamic interplay between lymphoid cells and stromal cells, which have become known as "lymphoid organizers." Second, correct spatiotemporal interaction between these cell populations is essential to generate the infrastructure for gut immune responses. Moreover, immune cells at the intestinal barrier are functionally modulated by stromal cells; one such example is the stromal cell-mediated differentiation of innate immune cells, including innate lymphoid cells and mast cells. Ultimately, mucosal stromal cells orchestrate the destinations of epithelial and immune cells to maintain intestinal immune homeostasis.


Asunto(s)
Células Epiteliales/inmunología , Homeostasis/inmunología , Células del Estroma/inmunología , Animales , Humanos , Inmunidad Innata/inmunología , Mucosa Intestinal/inmunología , Linfocitos/inmunología , Tejido Linfoide/inmunología , Mastocitos/inmunología
4.
Sci Rep ; 5: 15918, 2015 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-26522513

RESUMEN

Fucosylated glycans on the surface of epithelial cells (ECs) regulate intestinal homeostasis by serving as attachment receptors and a nutrient source for some species of bacteria. We show here that epithelial fucosylation in the ileum is negatively regulated by IL-10-producing CD4(+) T cells. The number of fucosylated ECs was increased in the ileum of mice lacking T cells, especially those expressing αß T cell receptor (TCR), CD4, and IL-10. No such effect was observed in mice lacking B cells. Adoptive transfer of αßTCR(+) CD4(+) T cells from normal mice, but not IL-10-deficient mice, normalized fucosylation of ECs. These findings suggest that IL-10-producing CD4(+) T cells contribute to the maintenance of the function of ECs by regulating their fucosylation.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Células Epiteliales/inmunología , Tracto Gastrointestinal/inmunología , Interleucina-4/inmunología , Traslado Adoptivo/métodos , Animales , Homeostasis/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos
5.
Science ; 345(6202): 1254009, 2014 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-25214634

RESUMEN

Fucosylation of intestinal epithelial cells, catalyzed by fucosyltransferase 2 (Fut2), is a major glycosylation mechanism of host-microbiota symbiosis. Commensal bacteria induce epithelial fucosylation, and epithelial fucose is used as a dietary carbohydrate by many of these bacteria. However, the molecular and cellular mechanisms that regulate the induction of epithelial fucosylation are unknown. Here, we show that type 3 innate lymphoid cells (ILC3) induced intestinal epithelial Fut2 expression and fucosylation in mice. This induction required the cytokines interleukin-22 and lymphotoxin in a commensal bacteria-dependent and -independent manner, respectively. Disruption of intestinal fucosylation led to increased susceptibility to infection by Salmonella typhimurium. Our data reveal a role for ILC3 in shaping the gut microenvironment through the regulation of epithelial glycosylation.


Asunto(s)
Fucosa/metabolismo , Inmunidad Innata , Mucosa Intestinal/inmunología , Linfocitos/inmunología , Microbiota/inmunología , Infecciones por Salmonella/inmunología , Salmonella typhimurium , Animales , Secuencia de Bases , Modelos Animales de Enfermedad , Fucosiltransferasas/genética , Fucosiltransferasas/metabolismo , Vida Libre de Gérmenes , Glicosilación , Células Caliciformes/enzimología , Células Caliciformes/inmunología , Células Caliciformes/microbiología , Íleon/enzimología , Íleon/inmunología , Íleon/microbiología , Interleucinas/inmunología , Mucosa Intestinal/enzimología , Mucosa Intestinal/microbiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Mutantes , Datos de Secuencia Molecular , Células de Paneth/enzimología , Células de Paneth/inmunología , Células de Paneth/microbiología , Infecciones por Salmonella/microbiología , Interleucina-22 , Galactósido 2-alfa-L-Fucosiltransferasa
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