PMID- 20829492
OWN - NLM
STAT- MEDLINE
DCOM- 20101028
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 107
IP  - 39
DP  - 2010 Sep 28
TI  - Effective shutdown in the expression of celiac disease-related wheat gliadin 
      T-cell epitopes by RNA interference.
PG  - 17023-8
LID - 10.1073/pnas.1007773107 [doi]
AB  - Celiac disease (CD) is an enteropathy triggered by the ingestion of gluten 
      proteins from wheat and similar proteins from barley and rye. The inflammatory 
      reaction is controlled by T cells that recognize gluten peptides in the context 
      of human leukocyte antigen (HLA) DQ2 or HLA-DQ8 molecules. The only available 
      treatment for the disease is a lifelong gluten-exclusion diet. We have used RNAi 
      to down-regulate the expression of gliadins in bread wheat. A set of hairpin 
      constructs were designed and expressed in the endosperm of bread wheat. The 
      expression of gliadins was strongly down-regulated in the transgenic lines. Total 
      gluten protein was extracted from transgenic lines and tested for ability to 
      stimulate four different T-cell clones derived from the intestinal lesion of CD 
      patients and specific for the DQ2-alpha-II, DQ2-gamma-VII, DQ8-alpha-I, and DQ8-gamma-I epitopes. 
      For five of the transgenic lines, there was a 1.5-2 log reduction in the amount 
      of the DQ2-alpha-II and DQ2-gamma-VII epitopes and at least 1 log reduction in the amount 
      of the DQ8-alpha-I and DQ8-gamma-I epitopes. Furthermore, transgenic lines were also 
      tested with two T-cell lines that are reactive with omega-gliadin epitopes. The total 
      gluten extracts were unable to elicit T-cell responses for three of the 
      transgenic wheat lines, and there were reduced responses for six of the 
      transgenic lines. This work shows that the down-regulation of gliadins by RNAi 
      can be used to obtain wheat lines with very low levels of toxicity for CD 
      patients.
FAU - Gil-Humanes, Javier
AU  - Gil-Humanes J
AD  - Instituto de Agricultura Sostenible, Consejo Superior de Investigaciones 
      Cientificas, E-14080 Cordoba, Spain.
FAU - Piston, Fernando
AU  - Piston F
FAU - Tollefsen, Stig
AU  - Tollefsen S
FAU - Sollid, Ludvig M
AU  - Sollid LM
FAU - Barro, Francisco
AU  - Barro F
LA  - eng
SI  - GENBANK/HM352557
SI  - GENBANK/HM352558
SI  - GENBANK/HM352559
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100909
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (RNA, Small Interfering)
RN  - 9007-90-3 (Gliadin)
SB  - IM
MH  - Base Sequence
MH  - Celiac Disease/*immunology
MH  - Cell Line
MH  - Epitopes, T-Lymphocyte/*genetics/immunology
MH  - Gliadin/*genetics/immunology
MH  - HLA-DQ Antigens/immunology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Nucleic Acid Conformation
MH  - Plants, Genetically Modified/genetics/*immunology
MH  - *RNA Interference
MH  - RNA, Small Interfering/chemistry/genetics
MH  - T-Lymphocytes/immunology
MH  - Triticum/genetics/*immunology
PMC - PMC2947919
COIS- The authors declare no conflict of interest.
EDAT- 2010/09/11 06:00
MHDA- 2010/10/29 06:00
PMCR- 2010/09/09
CRDT- 2010/09/11 06:00
PHST- 2010/09/11 06:00 [entrez]
PHST- 2010/09/11 06:00 [pubmed]
PHST- 2010/10/29 06:00 [medline]
PHST- 2010/09/09 00:00 [pmc-release]
AID - 1007773107 [pii]
AID - 201007773 [pii]
AID - 10.1073/pnas.1007773107 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):17023-8. doi: 
      10.1073/pnas.1007773107. Epub 2010 Sep 9.