Impact of intestinal ischemia-reperfusion on cytokine profile and enterocyte viability in human syngeneic intestinal transplantation

Kadry, Zakiyah; Roux‐Lombard, Pascale; Dayer, Jean‐Michel; Lieberman, Joshua M.; Marks, William H.; Dafoe, Donald C.; Crétin, Nathalie; Cighetti, Giuliana; Bühler, Léo H.; Charbonnet, Pierre; Morel, P

doi:10.1016/s0041-1345(00)01231-8

Cited by 3 publications

(1 citation statement)

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“…It has been suggested that the initial insult in gastroschisis is ischemic, secondary to a narrow abdominal wall defect (34), and the cytokine profile we obtained is consistent with the changes reported in the setting of intestinal ischemia-reperfusion injury (35). We speculate that the ischemic insult initiates an inflammatory environment, leading to recruitment and activation of T cells and eosinophils and ultimately resulting in bowel damage.…”

Section: Discussionsupporting

confidence: 88%

Heightened Immune Activation in Fetuses with Gastroschisis May Be Blocked by Targeting IL-5

Frascoli

Jeanty

Fleck

et al. 2016

The Journal of Immunology

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The development of the fetal immune system during pregnancy is a well-orchestrated process with important consequences for fetal and neonatal health, but prenatal factors that affect immune activation are poorly understood. We hypothesized that chronic fetal inflammation may lead to alterations in the development of the fetal immune system. To test this hypothesis, we examined neonates with gastroschisis, a congenital abdominal wall defect that leads to exposure of the fetal intestines to amniotic fluid, with resultant intestinal inflammation. We determined that patients with gastroschisis show high systemic levels of inflammatory cytokines and chemokines such as eotaxin, and earlier activation of CD4+ and CD8+ effector and memory T cells in the cord blood compared to controls. In addition, increased numbers of T cells and eosinophils infiltrate the serosa and mucosa of the inflamed intestines. Using a mouse model of gastroschisis, we observed higher numbers of eosinophils and both type 2 and type 3 innate lymphoid cells (ILC2 and ILC3), specifically in the portion of organs exposed to the amniotic fluid. Given the role of IL-5 produced by ILC2 in regulating eosinophil development and survival, we determined that maternal or fetal administration of the anti IL-5 neutralizing antibody, or a depleting antibody against ILCs, can both effectively reduce intestinal eosinophilia. Thus, a congenital anomaly causing chronic inflammation can alter the composition of circulating and tissue-resident fetal immune cells. Given the high rate of prenatal and neonatal complications in these patients, such changes have clinical significance and might become targets for fetal therapy.

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Section: Discussionsupporting

confidence: 88%