Critical role of intestinal interleukin-4 modulating regulatory T cells for desensitization, tolerance, and inflammation of food allergy.
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.OVA23-3, recombination...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5325285?pdf=render |
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| author | Haruyo Nakajima-Adachi Kyoko Shibahara Yoko Fujimura Jun Takeyama Erika Hiraide Akira Kikuchi Hitoshi Murakami Akira Hosono Tomonori Nochi Yoshio Wakatsuki Naoki Shimojo Shuichi Kaminogawa Ryuichiro Sato Hiroshi Kiyono Satoshi Hachimura |
| author_facet | Haruyo Nakajima-Adachi Kyoko Shibahara Yoko Fujimura Jun Takeyama Erika Hiraide Akira Kikuchi Hitoshi Murakami Akira Hosono Tomonori Nochi Yoshio Wakatsuki Naoki Shimojo Shuichi Kaminogawa Ryuichiro Sato Hiroshi Kiyono Satoshi Hachimura |
| author_sort | Haruyo Nakajima-Adachi |
| collection | DOAJ |
| description | 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.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.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.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. |
| first_indexed | 2024-04-14T07:11:23Z |
| format | Article |
| id | doaj.art-4e427ce4b9c94186ac305f008b0bbc22 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T07:11:23Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4e427ce4b9c94186ac305f008b0bbc222022-12-22T02:06:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017279510.1371/journal.pone.0172795Critical role of intestinal interleukin-4 modulating regulatory T cells for desensitization, tolerance, and inflammation of food allergy.Haruyo Nakajima-AdachiKyoko ShibaharaYoko FujimuraJun TakeyamaErika HiraideAkira KikuchiHitoshi MurakamiAkira HosonoTomonori NochiYoshio WakatsukiNaoki ShimojoShuichi KaminogawaRyuichiro SatoHiroshi KiyonoSatoshi HachimuraThe 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.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.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.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.http://europepmc.org/articles/PMC5325285?pdf=render |
| spellingShingle | Haruyo Nakajima-Adachi Kyoko Shibahara Yoko Fujimura Jun Takeyama Erika Hiraide Akira Kikuchi Hitoshi Murakami Akira Hosono Tomonori Nochi Yoshio Wakatsuki Naoki Shimojo Shuichi Kaminogawa Ryuichiro Sato Hiroshi Kiyono Satoshi Hachimura Critical role of intestinal interleukin-4 modulating regulatory T cells for desensitization, tolerance, and inflammation of food allergy. PLoS ONE |
| title | Critical role of intestinal interleukin-4 modulating regulatory T cells for desensitization, tolerance, and inflammation of food allergy. |
| title_full | Critical role of intestinal interleukin-4 modulating regulatory T cells for desensitization, tolerance, and inflammation of food allergy. |
| title_fullStr | Critical role of intestinal interleukin-4 modulating regulatory T cells for desensitization, tolerance, and inflammation of food allergy. |
| title_full_unstemmed | Critical role of intestinal interleukin-4 modulating regulatory T cells for desensitization, tolerance, and inflammation of food allergy. |
| title_short | Critical role of intestinal interleukin-4 modulating regulatory T cells for desensitization, tolerance, and inflammation of food allergy. |
| title_sort | critical role of intestinal interleukin 4 modulating regulatory t cells for desensitization tolerance and inflammation of food allergy |
| url | http://europepmc.org/articles/PMC5325285?pdf=render |
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