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NOD2 drives early IL-33-dependent expansion of group 2 innate lymphoid cells during Crohn's disease-like ileitis.
De Salvo, Carlo; Buela, Kristine-Ann; Creyns, Brecht; Corridoni, Daniele; Rana, Nitish; Wargo, Hannah L; Cominelli, Chiara L; Delaney, Peter G; Rodriguez-Palacios, Alexander; Cominelli, Fabio; Vermeire, Séverine; Pizarro, Theresa T.
Afiliación
  • De Salvo C; Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Buela KA; Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Creyns B; Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, and.
  • Corridoni D; Department of Chronic Diseases, Metabolism and Aging, TARGID, University Hospitals, KU Leuven, Leuven, Belgium.
  • Rana N; Department of Medicine and.
  • Wargo HL; Department of Digestive Health Research Institute, Case Western Reserve University, Cleveland, Ohio, USA.
  • Cominelli CL; Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Delaney PG; Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Rodriguez-Palacios A; Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Cominelli F; Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
  • Vermeire S; Department of Medicine and.
  • Pizarro TT; Department of Digestive Health Research Institute, Case Western Reserve University, Cleveland, Ohio, USA.
J Clin Invest ; 131(5)2021 03 01.
Article en En | MEDLINE | ID: mdl-33444291
ABSTRACT
Innate lymphoid cells (ILCs) are enriched at barrier surfaces, including the gastrointestinal tract. While most studies have focused on the balance between pathogenic group 1 ILCs (ILC1s) and protective ILC3s in maintaining gut homeostasis and during chronic intestinal inflammation, such as Crohn's disease (CD), less is known regarding ILC2s. Using an established murine model of CD-like ileitis, i.e., the SAMP1/YitFc (SAMP) mouse strain, we showed that ILC2s, compared with ILC1s and ILC3s, were increased within draining mesenteric lymph nodes and ilea of SAMP versus AKR (parental control) mice early, during the onset of disease. Gut-derived ILC2s from CD patients versus healthy controls were also increased and expanded, similarly to ILC1s, in greater proportion compared with ILC3s. Importantly, we report that the intracellular bacteria-sensing protein, nucleotide-binding oligomerization domaining-containing protein 2, encoded by Nod2, the first and strongest susceptibility gene identified for CD, promoted ILC2 expansion, which was dramatically reduced in SAMP mice lacking NOD2 and in SAMP mice raised under germ-free conditions. Furthermore, these effects occurred through a mechanism involving the IL-33/ST2 ligand-receptor pair. Collectively, our results indicate a functional link between NOD2 and ILC2s, regulated by the IL-33/ST2 axis, that mechanistically may contribute to early events leading to CD pathogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos / Transducción de Señal / Enfermedad de Crohn / Proteína Adaptadora de Señalización NOD2 / Interleucina-33 / Ileítis Límite: Animals Idioma: En Revista: J Clin Invest Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos / Transducción de Señal / Enfermedad de Crohn / Proteína Adaptadora de Señalización NOD2 / Interleucina-33 / Ileítis Límite: Animals Idioma: En Revista: J Clin Invest Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
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