Microbiota regulate the ability of lung dendritic cells to induce IgA class-switch recombination and generate protective gastrointestinal immune responses

Ruane, Darren; Chorny, Alejo; Lee, Haekyung; Faith, Jeremiah J.; Pandey, Gaurav; Shan, Meimei; Simchoni, Noa; Rahman, Adeeb; Garg, Aakash; Weinstein, Elena; Oropallo, Michael A.; Gaylord, Michelle; Ungaro, Ryan C.; Cunningham‐Rundles, Charlotte; Alexandropoulos, Konstantina; Mucida, Daniel; Mérad, Miriam; Cerutti, Andrea; Mehandru, Saurabh

doi:10.1084/jem.20150567

Cited by 98 publications

(90 citation statements)

References 98 publications

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“…IgA production [44,45]. Although mice with deletion of TGF-b signaling in B-cells (CD19-Cre Tgfbr2 fl/fl ) did not show signs of autoimmunity or colitis, CD19-Cre Tgfbr2 fl/fl mice showed B-cell hyperplasia in Peyer's patches and decreased B-cell responsiveness with complete serum IgA deficiency [45,46].…”

Section: Tgf-b In B-cells Mediates Iga Class-switch and Promotesmentioning

confidence: 99%

TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota

2017

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Inflammatory bowel disease (IBD) is defined as chronic intestinal inflammation, and includes ulcerative colitis and Crohn's disease. Multiple factors are involved in the pathogenesis of IBD, and the condition is characterized by aberrant mucosal immune reactions to intestinal microbes in genetically susceptible hosts. Transforming growth factor-b (TGF-b) is an immune-suppressive cytokine produced by many cell types and activated by integrins. Active TGF-b binds to its receptor and regulates mucosal immune reactions through the TGF-b signaling pathway. Dysregulated TGF-b signaling is observed in the intestines of IBD patients. TGF-b signal impairment in specific cell types, such as T-cells and dendritic cells, results in spontaneous colitis in mouse models. In addition, specific intestinal microbes contribute to immune homeostasis by modulating TGF-b production. In this review, we describe the role of TGF-b in intestinal immunity, focusing on immune cells, epithelium, and intestinal microbes. In addition, we present potential therapeutic strategies for IBD that target TGF-b.

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Section: Tgf-b In B-cells Mediates Iga Class-switch and Promotesmentioning

confidence: 99%

TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota

2017

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“…However, nasal immunization, which induces α4β1, L-sectin and CCR10, is generally not considered an effective approach for inducing SIgA in the gut. This notion has been challenged by a report indicating that NALT DCs possess the machinery for induction of RA and expression of α4β7+ on effector B cells, but stimulation by microbiota was required for these functions to develop (46). The sublingual route is used effectively for delivery of medication and allergen-specific immune therapy in humans and animals (47–50).…”

Section: Vaccine Adjuvants and Delivery Systems For Induction Of Mmentioning

confidence: 99%

Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems

Boyaka

2017

The Journal of Immunology

185

165

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Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chemical degradation in the harsh environment of mucosal surfaces and the enzymes of host or microbial origin. Production of SIgA is finely regulated and distinct T-independent and T-dependent mechanisms orchestrate immunoglobulin heavy chain α class switching and SIgA responses against commensal and pathogenic microbes. Most infectious pathogens enter the host via mucosal surfaces. To provide a first line of protection at these entry ports, vaccines are being developed to induce pathogen-specific SIgA in addition to systemic immunity achieved by injected vaccines. Mucosal or epicutaneous delivery of vaccines helps target the inductive sites for IgA responses. The efficacy of such vaccines relies on the identification/engineering of vaccine adjuvants capable of supporting the development of SIgA alongside systemic immunity and delivery systems that improve vaccine delivery to the targeted anatomic sites and immune cells.

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“…42,51,52 Upon TLR activation, epithelial and dendritic cells release B-cell activating factor ( BAFF ) and proliferation-inducing ligand ( APRIL ), thereby promoting T-cell independent IgA class switching. 53 These findings gave rise to the concept that T-independent secretory IgA production is important for protection against commensal intestinal microbes, while T-dependent secretory IgA are important for protection against pathogens.…”

Section: What Is the Impact Of The Microbiome On Ocular Immunity?mentioning

confidence: 99%

Impact of Microbiome on Ocular Health

2016

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The ocular surface is continuously exposed to the environment and, therefore, it is surprising that it harbors only few commensals with low degree of diversity. This unique aspect of the ocular surface physiology prompts the question whether there are core ocular commensal communities and how they affect ocular immunity. The purpose of this review is to provide an overview of what is known about the ocular surface commensals in health and disease and what we would like to learn in the near future. In addition, we discuss how microbiota at sites other than the eye may influence ocular immune responses. The information discussed in the review has been gathered using PubMed searches for literature published from January 1982 to December 2015.

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Microbiota regulate the ability of lung dendritic cells to induce IgA class-switch recombination and generate protective gastrointestinal immune responses

Abstract: Ruane et al. demonstrate a role for the microbiota in modulating protective immunity to intranasal vaccination via the ability of lung dendritic cells to induce B cell IgA class switching.

Cited by 98 publications

References 98 publications

TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota

TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota

Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems

Impact of Microbiome on Ocular Health

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