Intestinal Monocyte-Derived Macrophages Control Commensal-Specific Th17 Responses

Panea, Casandra; Farkas, Adam M.; Goto, Yoshiyuki; Abdollahi‐Roodsaz, Shahla; Lee, Carolyn; Koscsó, Balázs; Gowda, Kavitha; Hohl, Tobias M.; Bogunovic, Milena; Ivanov, Ivaylo I.

doi:10.1016/j.celrep.2015.07.040

Cited by 121 publications

(100 citation statements)

References 48 publications

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“…For example, monocyte-derived MHC2−hi APCs (28) contribute to the development of mucosal T H 17 cells, while Treg cells in the gut broadly require CD103+ cDCs (29). Recent work from our lab suggests that mucosal Treg development is also partially dependent on the CD11b+ fraction of CD103+ DCs in a monoclonal setting (30).…”

Section: Resultsmentioning

confidence: 99%

Antigen-Specific Development of Mucosal Foxp3+RORγt+ T Cells from Regulatory T Cell Precursors

Solomon

Hsieh

2016

The Journal of Immunology

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Foxp3+RORγt+ T cells have recently been characterized as an immunoregulatory population highly enriched in the colon lamina propria. However, their developmental origin and relation to RORγt− Treg and T H 17 cells remains unclear. Here, we use a fixed TCRβ system to show that the TCR repertoire of the Foxp3+RORγt+ population is mostly distinct compared to other colonic T cell subsets. However, a fraction of these TCRs are also found in the T H 17 subset, suggesting that TCR repertoire overlap may contribute to the reported ability of Foxp3+RORγt+ cells to regulate T H 17 immunity. Naïve transgenic T cells expressing a Foxp3+RORγt+ restricted TCR first acquire a Foxp3+RORγt− phenotype before co-expressing RORγt, suggesting that Foxp3+RORγt + cell development can occur via an RORγt− Treg intermediate.

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Section: Resultsmentioning

confidence: 99%

Antigen-Specific Development of Mucosal Foxp3+RORγt+ T Cells from Regulatory T Cell Precursors

Solomon

Hsieh

2016

The Journal of Immunology

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“…CX3CR1 + MNPs are involved in the induction of Th17 responses to intestinal bacteria (18) and are essential for the killing of Candida in the kidneys during systemic infection (19). Conversely, several studies have suggested a central role for IRF4-dependent CD11b + CD103 + DCs in intestinal Th17 cell differentiation, as well as Th17-induced bacterial and fungal clearance in the lung (12, 14).…”

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confidence: 99%

CX3CR1 ⁺ mononuclear phagocytes control immunity to intestinal fungi

Leonardi

Semon

et al. 2018

Science

230

219

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Intestinal fungi are an important component of the microbiota, and recent studies have unveiled their potential in modulating host immune homeostasis and inflammatory disease. Nonetheless, the mechanisms governing immunity to gut mycobiota remain unknown. We identified CX3CR1+ mononuclear phagocytes (MNPs) as essential for the initiation of innate and adaptive immune responses to intestinal fungi. CX3CR1+ MNPs express antifungal receptors and activate antifungal responses in a Syk dependent manner. Genetic ablation of CX3CR1+ MNPs led to changes in the gut fungal communities and to severe colitis that was rescued by antifungal treatment. A missense mutation in the gene encoding CX3CR1 led to impaired antifungal responses in Crohn’s Disease patients. These results unravel the role of CX3CR1+ MNPs as mediators of the interactions between intestinal mycobiota and host immunity during health and disease.

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“…Intestinal bacteria could also contribute to the activation of IL-17A response in the intestinal mucosa of active CD patients and in subjects unresponsive to the GFD experimental models [27] . Therefore, theoretically, intestinal bacteria could also contribute to the activation of IL-17A response in the intestinal mucosa of active CD patients and in subjects unresponsive to the GFD [28] .…”

Section: Introductionmentioning

confidence: 99%

Microbiome and Gluten

Sanz¹

2015

Ann Nutr Metab

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Celiac disease (CD) is a frequent chronic inflammatory enteropathy caused by gluten in genetically predisposed individuals that carry disease susceptibility genes (HLA-DQ2/8). These genes are present in about 30-40% of the general population, but only a small percentage of carriers develops CD. Gluten is the key environmental trigger of CD, but its intake does not fully explain disease onset; indeed, an increased number of cases experience gluten intolerance in late adulthood after many years of gluten exposure. Consequently, additional environmental factors seem to be involved in CD. Epidemiological studies indicate that common perinatal and early postnatal factors influence both CD risk and intestinal microbiota structure. Prospective studies in healthy infants at risk of developing CD also reveal that the HLA-DQ genotype, in conjunction with other environmental factors, influences the microbiota composition. Furthermore, CD patients have imbalances in the intestinal microbiota (dysbiosis), which are not fully normalized despite their adherence to a gluten-free diet. Therefore, it is hypothesized that the disease can promote dysbiosis that aggravates CD pathogenesis, and dysbiosis, in turn, can initiate and sustain inflammation through the expansion of proinflammatory pathobionts and decline of anti-inflammatory mutualistic bacteria. Studies in experimental models are also contributing to understand the role of intestinal bacteria and its interactions with a predisposed genotype in promoting CD. Advances in this area could aid in the development of microbiome-informed intervention strategies that optimize the partnership between the gut microbiota and host immunity for improving CD management.

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Intestinal Monocyte-Derived Macrophages Control Commensal-Specific Th17 Responses

Cited by 121 publications

References 48 publications

Antigen-Specific Development of Mucosal Foxp3+RORγt+ T Cells from Regulatory T Cell Precursors

Antigen-Specific Development of Mucosal Foxp3+RORγt+ T Cells from Regulatory T Cell Precursors

CX3CR1 ⁺ mononuclear phagocytes control immunity to intestinal fungi

Microbiome and Gluten

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Intestinal Monocyte-Derived Macrophages Control Commensal-Specific Th17 Responses

Cited by 121 publications

References 48 publications

Antigen-Specific Development of Mucosal Foxp3+RORγt+ T Cells from Regulatory T Cell Precursors

Antigen-Specific Development of Mucosal Foxp3+RORγt+ T Cells from Regulatory T Cell Precursors

CX3CR1 + mononuclear phagocytes control immunity to intestinal fungi

Microbiome and Gluten

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CX3CR1 ⁺ mononuclear phagocytes control immunity to intestinal fungi