Predominance of type 1 innate lymphoid cells in the rectal mucosa of patients with non-celiac wheat sensitivity: reversal after a wheat-free diet

Background: Non-celiac wheat sensitivity (NCWS) is defined as a reaction to ingested wheat after exclusion of celiac disease and wheat allergy. Since its pathogenesis is incompletely understood, we evaluated the inflammatory response in the rectal mucosa of patients with well-defined NCWS. Materials and 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 performed with 80 grams of wheat daily, cells were isolated from rectal biopsies and thoroughly characterized by FACS analysis for intracellular cytokines and surface markers. Results: Rectal biopsies from wheat challenged NCWS patients showed a significant mucosal CD45+ infiltrate consisted of CD3+ and CD3- lymphocytes, with these latter spontaneously producing more IFN- than IBS controls. About 30% of IFN--producing CD45+ cells were T-bet+, CD56-, NKP44- and CD117-, defining them as a type-1 innate lymphoid cells (ILC1). IFN--producing ILC1 cells significantly decreased in ten patients analysed two weeks after they resumed a wheat-free diet. Conclusion: These data indicate that in patients with active NCWS, IFN--producing ILC1 cells infiltrate rectal mucosa and support a role for this innate lymphoid cells population in the pathogenesis of NCWS.