Critical role of intestinal interleukin-4 modulating regulatory T cells for desensitization, tolerance, and inflammation of food allergyReport as inadecuate




Critical role of intestinal interleukin-4 modulating regulatory T cells for desensitization, tolerance, and inflammation of food allergy - Download this document for free, or read online. Document in PDF available to download.

Background and objective

The mechanism inducing either inflammation or tolerance to orally administered food allergens remains unclear. To investigate this we analyzed mouse models of food allergy OVA23-3 and tolerance DO11.10 D10, both of which express ovalbumin OVA-specific T-cell receptors.

Methods

OVA23-3, recombination activating gene RAG-2-deficient OVA23-3 R23-3, D10, and RAG-2-deficient D10 RD10 mice consumed a diet containing egg white EW diet for 2–28 days. Interleukin IL-4 production by CD4+ T cells was measured as a causative factor of enteropathy, and anti-IL-4 antibody was used to reveal the role of Foxp3+ OVA-specific Tregs aiTreg in this process.

Results

Unlike OVA23-3 and R23-3 mice, D10 and RD10 mice did not develop enteropathy and weight loss on the EW diet. On days 7–10, in EW-fed D10 and RD10 mice, splenic CD4+ T cells produced significantly more IL-4 than did those in the mesenteric lymph nodes MLNs; this is in contrast to the excessive IL-4 response in the MLNs of EW-fed OVA23-3 and R23-3 mice. EW-fed R23-3 mice had few aiTregs, whereas EW-fed RD10 mice had them in both tissues. Intravenous injections of anti-IL-4 antibody recovered the percentage of aiTregs in the MLNs of R23-3 mice. On day 28, in EW-fed OVA23-3 and R23-3 mice, expression of Foxp3 on CD4+ T cells corresponded with recovery from inflammation, but recurrence of weight loss was observed on restarting the EW diet after receiving the control-diet for 1 month. No recurrence developed in D10 mice.

Conclusions

Excessive IL-4 levels in the MLNs directly inhibited the induction of aiTregs and caused enteropathy. The aiTregs generated in the attenuation of T cell-dependent food allergic enteropathy may function differently than aiTregs induced in a tolerance model. Comparing the two models enables to investigate their aiTreg functions and to clarify differences between inflammation with subsequent desensitization versus tolerance.



Author: Haruyo Nakajima-Adachi , Kyoko Shibahara , Yoko Fujimura, Jun Takeyama, Erika Hiraide, Akira Kikuchi, Hitoshi Murakami, Akira Hos

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents