Study On The Genes Mediating Oral Tolerance In A Murine Model Of Allergic Asthma
碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 95 === Oral tolerance is defined as a state of immunological unresponsiveness to a specific antigen after exposure to that antigen via the enteric route. This characteristic phenomenon might be used as a potential treatment for allergic diseases such as asthma. Asthma...
Main Authors: | , |
---|---|
Other Authors: | |
Format: | Others |
Language: | zh-TW |
Published: |
2007
|
Online Access: | http://ndltd.ncl.edu.tw/handle/89785981586343924113 |
id |
ndltd-TW-095NTU05596016 |
---|---|
record_format |
oai_dc |
spelling |
ndltd-TW-095NTU055960162015-11-09T04:04:49Z http://ndltd.ncl.edu.tw/handle/89785981586343924113 Study On The Genes Mediating Oral Tolerance In A Murine Model Of Allergic Asthma 探討過敏性氣喘小鼠引發口服耐受性之相關基因 Shih-Yi Yu 游詩怡 碩士 國立臺灣大學 口腔生物科學研究所 95 Oral tolerance is defined as a state of immunological unresponsiveness to a specific antigen after exposure to that antigen via the enteric route. This characteristic phenomenon might be used as a potential treatment for allergic diseases such as asthma. Asthma is usually regarded as a hyper-responsive airway disease involving chronic inflammation. First, we established an animal model using OVA-T-cell receptor (OVA-TCR) transgenic mice with airway hyperresponsiveness, antigen-specific IgE production, and eosinophilia. The OVA-TCR can recognize the 323-339 peptide fragment of ovalbumin (OVA). In this study, oral tolerance was induced by tube-feeding transgenic mice with 0.5mg/day OVA protein daily, simultaneously sensitized by OVA protein with aluminum hydroxide. Oral-administered OVA protein (0.5mg/day for 5 or 10 consecutive days) resulted in significant lowered airway hypersensitivity as well as reduced inflammative cells infiltration, titer of serum OVA-specific IgE, IL-5 secretion in bronchoalveolar lavage fluid(BALF), and IL-4 secretion in splenocyte. Furthermore, the proliferation of OVA-specific splenocyte was inhibited by oral-administered OVA protein. Taken together, oral administration of low-dose OVA protein induced oral tolerance, inhibited both local and systemic type II helper T cell (Th2) response, and significantly relieved airway allergic hypersensitivity. The second goal of the present study was to evaluate the Peyer''s Patch (PP) gene expression in OVA-TCR transgenic mice after oral administration of OVA protein to induce specific immune tolerance. PP gene expression patterns were examined with Affymetrix Mouse GeneChip and further confirmed by real-time PCR. We detected the gene expression level on PP tissues, mesenteric lymph nodes (MLN), and CD4+CD25+ T cells derived from spleen after oral feeding of OVA protein (200mg/day, 20mg/day, and 0.5mg/day for 5 consecutive days). The results showed that transcription factor-associated genes, including foxp3, crem, and satb1, were highly expressed by the PP of the OVA-fed mice, and the growth suppression- and anergy- associated genes rbm10 and mterfd1 were elevated both in PP and CD4+CD25+ T cells derived from spleen after oral feeding of OVA protein. In addition to these genes, cd226 and crip3 were also up-regulated on PP and MLN upon OVA protein administration. Interestingly, most of these genes were mainly expressed in the B cells of PP. Moreover, as shown in some studies, naïve B cells are ineffective antigen-presenting cells (APC) and considered unable to activate naïve T cells, and even induced regulatory T cells inhibiting priming of fresh T cells in a contact-dependent manner in vitro. These results suggested that genes mediating oral tolerance were highly expressed in B cells of PP and may have a special mechanism to regulate immune tolerance. Bor-Luen Chiang 江伯倫 2007 學位論文 ; thesis 131 zh-TW |
collection |
NDLTD |
language |
zh-TW |
format |
Others
|
sources |
NDLTD |
description |
碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 95 === Oral tolerance is defined as a state of immunological unresponsiveness to a specific antigen after exposure to that antigen via the enteric route. This characteristic phenomenon might be used as a potential treatment for allergic diseases such as asthma. Asthma is usually regarded as a hyper-responsive airway disease involving chronic inflammation. First, we established an animal model using OVA-T-cell receptor (OVA-TCR) transgenic mice with airway hyperresponsiveness, antigen-specific IgE production, and eosinophilia. The OVA-TCR can recognize the 323-339 peptide fragment of ovalbumin (OVA). In this study, oral tolerance was induced by tube-feeding transgenic mice with 0.5mg/day OVA protein daily, simultaneously sensitized by OVA protein with aluminum hydroxide. Oral-administered OVA protein (0.5mg/day for 5 or 10 consecutive days) resulted in significant lowered airway hypersensitivity as well as reduced inflammative cells infiltration, titer of serum OVA-specific IgE, IL-5 secretion in bronchoalveolar lavage fluid(BALF), and IL-4 secretion in splenocyte. Furthermore, the proliferation of OVA-specific splenocyte was inhibited by oral-administered OVA protein. Taken together, oral administration of low-dose OVA protein induced oral tolerance, inhibited both local and systemic type II helper T cell (Th2) response, and significantly relieved airway allergic hypersensitivity.
The second goal of the present study was to evaluate the Peyer''s Patch (PP) gene expression in OVA-TCR transgenic mice after oral administration of OVA protein to induce specific immune tolerance. PP gene expression patterns were examined with Affymetrix Mouse GeneChip and further confirmed by real-time PCR. We detected the gene expression level on PP tissues, mesenteric lymph nodes (MLN), and CD4+CD25+ T cells derived from spleen after oral feeding of OVA protein (200mg/day, 20mg/day, and 0.5mg/day for 5 consecutive days). The results showed that transcription factor-associated genes, including foxp3, crem, and satb1, were highly expressed by the PP of the OVA-fed mice, and the growth suppression- and anergy- associated genes rbm10 and mterfd1 were elevated both in PP and CD4+CD25+ T cells derived from spleen after oral feeding of OVA protein. In addition to these genes, cd226 and crip3 were also up-regulated on PP and MLN upon OVA protein administration. Interestingly, most of these genes were mainly expressed in the B cells of PP. Moreover, as shown in some studies, naïve B cells are ineffective antigen-presenting cells (APC) and considered unable to activate naïve T cells, and even induced regulatory T cells inhibiting priming of fresh T cells in a contact-dependent manner in vitro. These results suggested that genes mediating oral tolerance were highly expressed in B cells of PP and may have a special mechanism to regulate immune tolerance.
|
author2 |
Bor-Luen Chiang |
author_facet |
Bor-Luen Chiang Shih-Yi Yu 游詩怡 |
author |
Shih-Yi Yu 游詩怡 |
spellingShingle |
Shih-Yi Yu 游詩怡 Study On The Genes Mediating Oral Tolerance In A Murine Model Of Allergic Asthma |
author_sort |
Shih-Yi Yu |
title |
Study On The Genes Mediating Oral Tolerance In A Murine Model Of Allergic Asthma |
title_short |
Study On The Genes Mediating Oral Tolerance In A Murine Model Of Allergic Asthma |
title_full |
Study On The Genes Mediating Oral Tolerance In A Murine Model Of Allergic Asthma |
title_fullStr |
Study On The Genes Mediating Oral Tolerance In A Murine Model Of Allergic Asthma |
title_full_unstemmed |
Study On The Genes Mediating Oral Tolerance In A Murine Model Of Allergic Asthma |
title_sort |
study on the genes mediating oral tolerance in a murine model of allergic asthma |
publishDate |
2007 |
url |
http://ndltd.ncl.edu.tw/handle/89785981586343924113 |
work_keys_str_mv |
AT shihyiyu studyonthegenesmediatingoraltoleranceinamurinemodelofallergicasthma AT yóushīyí studyonthegenesmediatingoraltoleranceinamurinemodelofallergicasthma AT shihyiyu tàntǎoguòmǐnxìngqìchuǎnxiǎoshǔyǐnfākǒufúnàishòuxìngzhīxiāngguānjīyīn AT yóushīyí tàntǎoguòmǐnxìngqìchuǎnxiǎoshǔyǐnfākǒufúnàishòuxìngzhīxiāngguānjīyīn |
_version_ |
1718126510568636416 |