IL-22BP is produced by eosinophils in human gut and blocks IL-22 protective actions during colitis

Martin, Jérôme C.; Bériou, Gaëlle; Heslan, Michèle; Bossard, Céline; Jarry, Anne; Abidi, Ahmed; Hulin, Philippe; Ménoret, Séverine; Thinard, Reynald; Anegón, Ignacio; Jacqueline, Cédric; Lardeux, Bernard; Halary, Franck; Renauld, Jean‐Christophe; Bourreille, Arnaud; Josien, Régis

doi:10.1038/mi.2015.83

Cited by 80 publications

(108 citation statements)

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“…An exception to this is colonic DCs which produce high levels regardless of their maturation state [24]. Reports of other sources of IL-22BP include macrophages, epithelial cells and more recently, eosinophils [11, 19, 25–27]. …”

Section: Introductionmentioning

confidence: 99%

Biological and pathological activities of interleukin-22

et al. 2016

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Interleukin (IL)-22, a member of the IL-10 family, is a cytokine secreted by several types of immune cells including IL-22+CD4+ T cells (Th22) and IL-22 expressing innate leukocytes (ILC22). Recent studies have demonstrated that IL-22 is a key component in mucosal barrier defense, tissue repair, epithelial cell survival and proliferation. Furthermore, accumulating evidence has defined both protective and pathogenic properties of IL-22 in a number of conditions including autoimmune disease, infection and malignancy. In this Review we summarize the expression and signaling pathway and functional characteristics of the IL-22 and IL-22 receptor axis in physiological and pathological scenarios, and discuss the potential to target IL-22 signaling to treat human diseases.

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Section: Introductionmentioning

confidence: 99%

Biological and pathological activities of interleukin-22

et al. 2016

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“…Retinoic acid promotes secretion of interleukin 22 , known to promote epithelial cell proliferation and healing, restore tight junctions, and increase mucus production from goblet cells. 14 Vitamin A is required for normal immune function and for the development of immune tolerance in the intestine. 4 In human studies and in animal models, vitamin A deficiency increases gut permeability, which can be improved by vitamin A supplementation.…”

Section: Introductionmentioning

confidence: 99%

Lower levels of vitamin A are associated with increased gastrointestinal graft-versus-host disease in children

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Khandelwal

Dandoy

et al. 2017

Blood

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• Vitamin A levels below the median at day 30 posttransplant are associated with increased cumulative incidence of GI GVHD in children.• Potential mechanisms include increased intestinal permeability and increased lymphocyte homing to the intestine.Vitamin A promotes development of mucosal tolerance and enhances differentiation of regulatory T cells. Vitamin A deficiency impairs epithelial integrity, increasing intestinal permeability. We hypothesized that higher vitamin A levels would reduce the risk of graftversus-host disease (GVHD) through reduced gastrointestinal (GI) permeability, reduced mucosal injury, and reduced lymphocyte homing to the gut. We tested this hypothesis in a cohort study of 114 consecutive patients undergoing allogeneic stem cell transplant. Free vitamin A levels were measured in plasma at day 30 posttransplant. GI GVHD was increased in patients with vitamin A levels below the median (38% vs 12.4% at 100 days, P 5 .0008), as was treatment-related mortality (17.7% vs 7.4% at 1 year, P 5 .03). Bloodstream infections were increased in patients with vitamin A levels below the median (24% vs 8% at 1 year, P 5 .03), supporting our hypothesis of increased intestinal permeability. The GI mucosal intestinal fatty acid-binding protein was decreased after transplant, confirming mucosal injury, but was not correlated with vitamin A levels, indicating that vitamin A did not protect against mucosal injury. Expression of the gut homing receptor CCR9 on T-effector memory cells 30 days after transplant was increased in children with vitamin A levels below the median (r 5 20.34, P 5 .03). Taken together, these data support our hypothesis that low levels of vitamin A actively promote GI GVHD and are not simply a marker of poor nutritional status or a sicker patient. Vitamin A supplementation might improve transplant outcomes. (Blood. 2017;129(20):2801-2807

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“…TRM amongst patients that developed acute GI GVHD IL-22 levels above the median was 46.9% compared to patients with IL-22 levels below the median of 20% at 1 year, p=0.6, Figure 1B. IL-22 binding protein (IL-22BP) is a soluble, potent inhibitor of IL-22 and is thought to regulate its downstream effects and has been found to be enhanced during active colitis of patients with IBD. (11,12) We hypothesized that IL-22BP levels would be elevated in patients with GI GVHD and that these levels would be inversely correlated with IL-22 levels. IL-22BP levels at day 30 post-transplant had a negative correlation with IL-22 levels at day 30 post-transplant (r=-0.2, p=0.03) but had no association with the development of GI GVHD.…”

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confidence: 99%