title: Predominance of Type 1 Innate Lymphoid Cells in the Rectal Mucosa of Patients With Non-Celiac Wheat Sensitivity: Reversal After a Wheat-Free Diet.
abstract: OBJECTIVE
  Non-celiac wheat sensitivity (NCWS) is defined as a reaction to ingested wheat after exclusion of celiac disease and wheat allergy. As its pathogenesis is incompletely understood, we evaluated the inflammatory response in the rectal mucosa of patients with well-defined NCWS.
  
  
  METHODS
  The prospective study included 22 patients with irritable bowel syndrome (IBS)-like clinical presentation, diagnosed with NCWS by double-blind placebo-controlled challenge. Eight IBS patients not improving on wheat-free diet were used as controls. Two weeks after oral challenge was performed with 80 grams of wheat daily, cells were isolated from rectal biopsies and thoroughly characterized by fluorescence-activated cell sorting analysis for intracellular cytokines and surface markers.
  
  
  RESULTS
  Rectal biopsies from wheat-challenged NCWS patients showed that a significant mucosal CD45(+) infiltrate consisted of CD3(+) and CD3(-) lymphocytes, with the latter spontaneously producing more interferon (IFN)-γ than IBS controls. About 30% of IFN-γ-producing CD45(+) cells were T-bet(+), CD56(-), NKP44(-), and CD117(-), defining them as a type-1 innate lymphoid cells (ILC1). IFN-γ-producing ILC1 cells significantly decreased in 10 patients analyzed 2 weeks after they resumed a wheat-free diet.
  
  
  CONCLUSIONS
  These data indicate that, in patients with active NCWS, IFN-γ-producing ILC1 cells infiltrate rectal mucosa and support a role for this innate lymphoid cell population in the pathogenesis of NCWS.
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy.|Dipartimento di Biopatologia e Biotecnologie Mediche (DIBIMED), University of Palermo, Palermo, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Di Liberto
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Mansueto
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: D'Alcamo
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy.|Dipartimento di Biopatologia e Biotecnologie Mediche (DIBIMED), University of Palermo, Palermo, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Lo Pizzo
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy.|Dipartimento di Biopatologia e Biotecnologie Mediche (DIBIMED), University of Palermo, Palermo, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Lo Presti
authors.affiliation: Surgery Department, University of Palermo, Palermo, Italy.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Geraci
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fayer
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy.|Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Guggino
authors.affiliation: Pediatric Gastroenterology, ARNAS Di Cristina Hospital, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Iacono
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy.|Dipartimento di Biopatologia e Biotecnologie Mediche (DIBIMED), University of Palermo, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
authors.affiliation: Dipartimento Biomedico di Medicina Interna e Specialistica (DIBIMIS), University of Palermo, Palermo, Italy.|Internal Medicine, Giovanni Paolo II Hospital, Sciacca (ASP Agrigento), Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Carroccio