Food antigen-induced immune responses in Crohn’s disease patients and experimental colitis mice

Abstract

BackgroundIn Crohn’s disease (CD), the involvement of food antigens in immune responses remains unclear. The objective of this study was to detect immune responses against food antigens in CD patients and examine the mechanism in a mouse model of colitis.MethodsWe enrolled 98 CD patients, 50 ulcerative colitis patients, and 52 healthy controls (HCs) to compare the levels of serum immunoglobulin (Ig)Gs against 88 foods. The presence of serum IgGs against foods was also examined in interleukin (IL)-10 knockout (KO) mice in which CD4+ T cell activation by antigenic food protein was assessed. Mice transferred with IL-10 KO cells received diets with or without food antigens, and the development of colitis was evaluated.ResultsThe prevalence of IgGs against various foods, especially vegetables, grains, and nuts, was significantly higher in CD patients than in HCs. Similarly, the prevalence of IgGs against food proteins was higher in IL-10 KO mice than in BALB/c mice. Beta-conglycinin, identified as an antigenic food proteins in IL-10 KO mice, induced CD4+ T cell production of interferon-γ and IL-17 through dendritic cell antigen presentation. Elimination of the food antigens ameliorated the development of colitis in mice without altering the composition of their intestinal microbiota.ConclusionsIn CD colitis mice, intestinal inflammation via CD4+ T cell hyperactivation was induced by food antigens associated with high serum IgG levels and was ameliorated by the elimination of food antigens. This disrupted immunological tolerance to food antigen, which might act as an exacerbating factor, remains to be elucidated in CD patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-014-0981-8) contains supplementary material, which is available to authorized users.

Intestinal development and homeostasis require activation and apoptosis of diet-reactive T cells

“…In contrast, the majority of LP DCs express CX 3 CR1, are CD103 + , and capture antigen from the intestinal lumen via transepithelial dendrites (34). In the presence of TGF-β and retinoic acid, LP-derived antigens (3). In this context, clinical observations have suggested lymphoid follicles as the initial site of inflammation in patients with CD, and that peak frequency of CD correlates with peak number of PPs at an age between 15 and 25 years (46)(47)(48).…”

“…Immunological tolerance to environmental factors such as intestinal bacteria and food antigens is an active, multilayered process, and its breakdown leads to hyperactivation of mucosal T and B cells and subsequent development of intestinal pathologies (1)(2)(3). Successful dietary intervention therapies in patients suffering from celiac disease, food allergies, and inflammatory bowel disease (IBD) demonstrate that diet contains immunologically relevant antigens (4)(5)(6)).…”

Gastrointestinal mucosal barrier function and diseases

“…The intestinal mucosal barrier is important in the regulation of the chaotic invasion of bacterial flora food antigens from the mucosal surface [98,99]. The regulation of humoral factors from the luminal side is also important in controlling the immune system in the intestine.…”

Frontline Science: TLR3 activation inhibits food allergy in mice by inducing IFN-γ+ Foxp3+ regulatory T cells

“…The clinical symptoms of FA vary greatly in individual attacks; some FA patients only show slight abdominal uncomfortable, whereas in some cases, FA attack may evoke the life‐threatening anaphylactic shock . On the other hand, the FAs are also involved in the pathogenesis of inflammatory bowel disease . The therapeutic effects of FA are unsatisfactory currently .…”