Protective mucosal immunity mediated by epithelial CD1d and IL-10

Olszak, Torsten; Neves, Joana F.; Dowds, C. Marie; Baker, Kristi; Glickman, Jonathan N.; Davidson, Nicholas O.; Lin, Chyuan Sheng; Jobin, Christian; Brand, Stephan; Sotlar, Karl; Wada, Koichiro; Katayama, Kazufumi; Nakajima, Atsushi; Mizuguchi, Hiroyuki; Kawasaki, Kunito; Nagata, Kazuhiro; Müller, Werner; Snapper, Scott B.; Schreiber, Stefan; Kaser, Arthur; Zeißig, Sebastian; Blumberg, Richard S.

doi:10.1038/nature13150

Cited by 173 publications

(172 citation statements)

References 40 publications

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“…Previous studies have shown that engagement of CD1d results in secretion of cytokines by both professional and unconventional APCs including IL‐10 secreted by IEC and IL‐12 by DCs and monocytes 21, 22. Consequently, engagement of epithelial CD1d renders protective effects in mouse models of IBD, while CD1d‐mediated production of IL‐12 by APCs leads to protection against viral infection 14, 23. To study whether CD1d could regulate ILC3 function, we performed antibody‐mediated cross‐linking of CD1d on ILC3s and measured changes in the expression of IL22 , IL17A, LTA and LTB (cytokines typically produced by ILC3s) as well as TNFSF13B (BAFF), TNFSF1 3 (APRIL) and CD40LG (CD40L; factors by which ILC3s modulate B‐cell function 28; Figs 3C and EV5).…”

Section: Resultsmentioning

confidence: 99%

“…Surface CD1d was cross‐linked by incubation of ILC3s with anti‐CD1d antibody (clone 1B1) followed by goat anti‐rat IgG as described 14, 21. In some experiments, cells were incubated with recombinant IL‐23 (100 ng/ml, Biolegend) or IL‐1β (100 ng/ml, Biolegend) and/or anti‐CD1d.…”

Section: Methodsmentioning

confidence: 99%

“…For instance, iNKT cell activation in response to glycolipid recognition results in CD40 ligand‐dependent maturation of dendritic cells (DC), favouring cross‐presentation and enhancing CD4, CD8 and B‐cell responses 18, 19, 20. Remarkably, engagement of CD1d is sufficient to induce activation and secretion of cytokines by both professional (DCs, monocytes) and unconventional (intestinal epithelial cells; IECs) APCs resulting in modulation of immunity in homeostasis and inflammation 14, 21, 22, 23. For example, ligation of CD1d in IEC leads to secretion of IL‐10 rendering protective effects in murine models of inflammatory bowel disease (IBD) 14, 21.…”

Section: Introductionmentioning

confidence: 99%

“…Remarkably, engagement of CD1d is sufficient to induce activation and secretion of cytokines by both professional (DCs, monocytes) and unconventional (intestinal epithelial cells; IECs) APCs resulting in modulation of immunity in homeostasis and inflammation 14, 21, 22, 23. For example, ligation of CD1d in IEC leads to secretion of IL‐10 rendering protective effects in murine models of inflammatory bowel disease (IBD) 14, 21.…”

Section: Introductionmentioning

confidence: 99%

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CD 1d‐mediated activation of group 3 innate lymphoid cells drives IL ‐22 production

et al. 2016

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Innate lymphoid cells (ILCs) are a heterogeneous family of immune cells that play a critical role in a variety of immune processes including host defence against infection, wound healing and tissue repair. Whether these cells are involved in lipid‐dependent immunity remains unexplored. Here we show that murine ILCs from a variety of tissues express the lipid‐presenting molecule CD1d, with group 3 ILCs (ILC3s) showing the highest level of expression. Within the ILC3 family, natural cytotoxicity triggering receptor (NCR)− CCR6+ cells displayed the highest levels of CD1d. Expression of CD1d on ILCs is functionally relevant as ILC3s can acquire lipids in vitro and in vivo and load lipids on CD1d to mediate presentation to the T‐cell receptor of invariant natural killer T (iNKT) cells. Conversely, engagement of CD1d in vitro and administration of lipid antigen in vivo induce ILC3 activation and production of IL‐22. Taken together, our data expose a previously unappreciated role for ILCs in CD1d‐mediated immunity, which can modulate tissue homeostasis and inflammatory responses.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CD 1d‐mediated activation of group 3 innate lymphoid cells drives IL ‐22 production

et al. 2016

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“…It is tempting to speculate that intestinal macrophages in the GI tract following IL-1α exposure to the chorioamnion/skin might be responsible for the accumulation of T cells in the fetal gut. 36 This intestinal immune response at 6 days after IL-1α administration to the chorioamnion/skin appeared to have an anti-inflammatory character as upregulated mRNA levels of IL-10, a cytokine that has central role in maintaining gut wall integrity, 37,38 were detected and associated with the absence of epithelial damage in the fetal ileum.…”

Section: Il-1α-driven Fetal Gut Inflammationmentioning

confidence: 99%

Selective IL-1α exposure to the fetal gut, lung, and chorioamnion/skin causes intestinal inflammatory and developmental changes in fetal sheep

Nikiforou

Kemp

Gorp

et al. 2016

Laboratory Investigation

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Chorioamnionitis, caused by intra-amniotic exposure to bacteria and their toxic components, is associated with fetal gut inflammation and mucosal injury. In a translational ovine model, we have shown that these adverse intestinal outcomes to chorioamnionitis were the combined result of local gut and pulmonary-driven systemic immune responses. Chorioamnionitis-induced gut inflammation and injury was largely prevented by inhibiting interleukin-1 (IL-1) signaling. Therefore, we investigated whether local (gut-derived) IL-1α signaling or systemic IL-1α-driven immune responses (lung or chorioamnion/skin-derived) were sufficient for intestinal inflammation and mucosal injury in the course of chorioamnionitis. Fetal surgery was performed in sheep to isolate the lung, gastrointestinal tract, and chorioamnion/skin, and IL-1α or saline was given into the trachea, stomach, or amniotic cavity 1 or 6 days before preterm delivery. Selective IL-1α exposure to the lung, gut, or chorioamnion/skin increased the CD3+ cell numbers in the fetal gut. Direct IL-1α exposure to the gut impaired intestinal zonula occludens protein-1 expression, induced villus atrophy, changed the expression pattern of intestinal fatty acid-binding protein along the villus, and increased the CD68, IL-1, and TNF-α mRNA levels in the fetal ileum. With lung or chorioamnion/skin exposure to IL-1α, intestinal inflammation was associated with increased numbers of blood leukocytes without induction of intestinal injury or immaturity. We concluded that local IL-1α signaling was required for intestinal inflammation, disturbed gut maturation, and mucosal injury in the context of chorioamnionitis. Intrauterine infection is the most frequent cause of preterm birth 1 before 28 weeks of gestation. 2 Chorioamnionitis, which is commonly caused by intrauterine bacterial infection, is defined as an inflammation of the fetal membranes, amniotic fluid and placenta. [3][4][5] Bacterial infection of the amniotic cavity results in direct exposure of the lung (by fetal breathing), gastrointestinal tract (by swallowing), skin, and chorioamnion to bacteria and their inflammatory components in the contaminated amniotic fluid. The fetal inflammatory response to chorioamnionitis is associated with multiorgan dysfunction, 6,7 which increase the incidence of periventricular leukomalacia, 8 bronchopulmonary dysplasia, 9 and necrotizing enterocolitis. 10,11 We have used a translational ovine model of chorioamnionitis to investigate the impact of intrauterine inflammation on fetal organs. Using this model, we have shown that intraamniotic (IA) delivery of Escherichia coli lipopolysaccharide (LPS) resulted in an acute inflammatory response in the chorioamnion and increased the influx of inflammatory cells in the respiratory tract within 5 h. 12,13 These immune alterations were rapidly followed by systemic inflammation at the same time point and fetal skin inflammation 12 h after LPS exposure. 13,14 The first signs of intestinal inflammation were detected 2 days after IA delivery of LPS, an...

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Characterization and Functional Analysis of Mouse Semi‐invariant Natural T Cells

et al. 2017

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Semi-invariant natural killer T (iNKT) cells are CD1d-restricted innate-like lymphocytes that recognize lipid agonists. Activated iNKT cells have immunoregulatory properties. Human and mouse iNKT cell functions elicited by different glycolipid agonists are highly conserved, making the mouse an excellent animal model for understanding iNKT cell biology in vivo. This unit describes basic methods for the characterization and quantification (see Basic Protocol 1) and functional analysis of mouse iNKT cells in vivo or in vitro. This unit also contains protocols that describe enrichment and purification of iNKT cells, generation of CD1d tetramer, and lipid antigen loading onto cell-bound and soluble CD1d for activation of NKT cell hybridomas. © 2017 by John Wiley & Sons, Inc.

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Protective mucosal immunity mediated by epithelial CD1d and IL-10

Cited by 173 publications

References 40 publications

CD 1d‐mediated activation of group 3 innate lymphoid cells drives IL ‐22 production

CD 1d‐mediated activation of group 3 innate lymphoid cells drives IL ‐22 production

Selective IL-1α exposure to the fetal gut, lung, and chorioamnion/skin causes intestinal inflammatory and developmental changes in fetal sheep

Characterization and Functional Analysis of Mouse Semi‐invariant Natural T Cells

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