Altered generation of induced regulatory T cells in the FVB.mdr1a−/− mouse model of colitis
The FVB. mdr1a −/− mouse, lacking the small molecule pump P-glycoprotein (P-gp), is a commonly used model for the study of spontaneous T cell–mediated colitis. In addition, MDR1 polymorphisms and P-gp deficiency in humans have been linked to the development of ulcerative colitis. We now demonstrate...
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| Veröffentlicht in: | Mucosal immunology 2013-03, Vol.6 (2), p.309-323 |
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| creator | Tanner, S M Staley, E M Lorenz, R G |
| description | The FVB.
mdr1a
−/−
mouse, lacking the small molecule pump P-glycoprotein (P-gp), is a commonly used model for the study of spontaneous T cell–mediated colitis. In addition,
MDR1
polymorphisms and P-gp deficiency in humans have been linked to the development of ulcerative colitis. We now demonstrate that mice with P-gp deficiency have decreased levels of Foxp3
+
regulatory T cells (Tregs) in the intestinal lamina propria. This decrease is not due to either increased Treg apoptosis, altered Treg trafficking, or enhanced Treg plasticity to become Foxp3
+
IL-17
+
cells. Instead, P-gp deficiency appears to restrict the development of induced Treg cells (iTregs), as fewer Foxp3
+
iTregs developed from naive FVB.
mdr1a
−/−
T cells both upon transforming growth factor-β (TGF-β) treatment
in vitro
and after adoptive transfer into FVB.
rag2
−/−
recipients. Rather,
in vitro
TGF-β treatment results in a IL-17
+
CD4
+
T cell. This failure of iTregs to develop explains the decrease in Foxp3
+
Tregs in the FVB.
mdr1a
−/−
intestine, representing a need to investigate this novel disease mechanism in human inflammatory bowel disease patients with
MDR1
polymorphisms. |
| doi_str_mv | 10.1038/mi.2012.73 |
| format | Article |
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mdr1a
−/−
mouse, lacking the small molecule pump P-glycoprotein (P-gp), is a commonly used model for the study of spontaneous T cell–mediated colitis. In addition,
MDR1
polymorphisms and P-gp deficiency in humans have been linked to the development of ulcerative colitis. We now demonstrate that mice with P-gp deficiency have decreased levels of Foxp3
+
regulatory T cells (Tregs) in the intestinal lamina propria. This decrease is not due to either increased Treg apoptosis, altered Treg trafficking, or enhanced Treg plasticity to become Foxp3
+
IL-17
+
cells. Instead, P-gp deficiency appears to restrict the development of induced Treg cells (iTregs), as fewer Foxp3
+
iTregs developed from naive FVB.
mdr1a
−/−
T cells both upon transforming growth factor-β (TGF-β) treatment
in vitro
and after adoptive transfer into FVB.
rag2
−/−
recipients. Rather,
in vitro
TGF-β treatment results in a IL-17
+
CD4
+
T cell. This failure of iTregs to develop explains the decrease in Foxp3
+
Tregs in the FVB.
mdr1a
−/−
intestine, representing a need to investigate this novel disease mechanism in human inflammatory bowel disease patients with
MDR1
polymorphisms.</description><identifier>ISSN: 1933-0219</identifier><identifier>EISSN: 1935-3456</identifier><identifier>DOI: 10.1038/mi.2012.73</identifier><identifier>PMID: 22874899</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/208/457/649 ; 631/250/1619/554/1898/1271 ; 692/699/249/2510/257/1389 ; Allergology ; Animals ; Antibodies ; Apoptosis ; ATP Binding Cassette Transporter, Subfamily B - deficiency ; ATP Binding Cassette Transporter, Subfamily B - genetics ; Biomedical and Life Sciences ; Biomedicine ; CD4 Antigens - metabolism ; Cell Movement - immunology ; Colitis - genetics ; Colitis - immunology ; Disease Models, Animal ; Forkhead Transcription Factors - metabolism ; Gastroenterology ; Immunology ; Interleukin-2 Receptor alpha Subunit - metabolism ; Intestinal Mucosa - metabolism ; Intestines - immunology ; Male ; Mice ; Mice, Knockout ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - metabolism ; Transforming Growth Factor beta - pharmacology</subject><ispartof>Mucosal immunology, 2013-03, Vol.6 (2), p.309-323</ispartof><rights>Society for Mucosal Immunology 2013</rights><rights>Copyright Nature Publishing Group Mar 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-5966f72b43348c98217c1d90d25982ae2b69ee12c6454fa499850949d0524bf43</citedby><cites>FETCH-LOGICAL-c442t-5966f72b43348c98217c1d90d25982ae2b69ee12c6454fa499850949d0524bf43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1783037791?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22874899$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tanner, S M</creatorcontrib><creatorcontrib>Staley, E M</creatorcontrib><creatorcontrib>Lorenz, R G</creatorcontrib><title>Altered generation of induced regulatory T cells in the FVB.mdr1a−/− mouse model of colitis</title><title>Mucosal immunology</title><addtitle>Mucosal Immunol</addtitle><addtitle>Mucosal Immunol</addtitle><description>The FVB.
mdr1a
−/−
mouse, lacking the small molecule pump P-glycoprotein (P-gp), is a commonly used model for the study of spontaneous T cell–mediated colitis. In addition,
MDR1
polymorphisms and P-gp deficiency in humans have been linked to the development of ulcerative colitis. We now demonstrate that mice with P-gp deficiency have decreased levels of Foxp3
+
regulatory T cells (Tregs) in the intestinal lamina propria. This decrease is not due to either increased Treg apoptosis, altered Treg trafficking, or enhanced Treg plasticity to become Foxp3
+
IL-17
+
cells. Instead, P-gp deficiency appears to restrict the development of induced Treg cells (iTregs), as fewer Foxp3
+
iTregs developed from naive FVB.
mdr1a
−/−
T cells both upon transforming growth factor-β (TGF-β) treatment
in vitro
and after adoptive transfer into FVB.
rag2
−/−
recipients. Rather,
in vitro
TGF-β treatment results in a IL-17
+
CD4
+
T cell. This failure of iTregs to develop explains the decrease in Foxp3
+
Tregs in the FVB.
mdr1a
−/−
intestine, representing a need to investigate this novel disease mechanism in human inflammatory bowel disease patients with
MDR1
polymorphisms.</description><subject>631/208/457/649</subject><subject>631/250/1619/554/1898/1271</subject><subject>692/699/249/2510/257/1389</subject><subject>Allergology</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>ATP Binding Cassette Transporter, Subfamily B - deficiency</subject><subject>ATP Binding Cassette Transporter, Subfamily B - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>CD4 Antigens - metabolism</subject><subject>Cell Movement - immunology</subject><subject>Colitis - genetics</subject><subject>Colitis - immunology</subject><subject>Disease Models, Animal</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Gastroenterology</subject><subject>Immunology</subject><subject>Interleukin-2 Receptor alpha Subunit - metabolism</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestines - immunology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>Transforming Growth Factor beta - pharmacology</subject><issn>1933-0219</issn><issn>1935-3456</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkctO3DAUhq2qqMC0mz5AFambCpTBt_iyQRoQA0hI3dBuLY9zMhglMbWTSrwBax6RJ8FhAFG68PV8-s_59SP0leA5wUwddH5OMaFzyT6gHaJZVTJeiY9Pd1ZiSvQ22k3pGmOBccU-oW1KleRK6x1kFu0AEepiDT1EO_jQF6EpfF-PLv9GWI-tHUK8LS4LB22bcqkYrqBY_j6ad3Uk9uHu_iCvogtjgrzX0E4KLrR-8Okz2mpsm-DL8zlDv5Ynl8dn5cXP0_PjxUXpOKdDWWkhGklXnDGunFaUSEdqjWta5YcFuhIagFAneMUby7VWFdZc17iifNVwNkOHG92bcdVB7aAfom3NTfSdjbcmWG_-rfT-yqzDX8OEFFroLPDjWSCGPyOkwXQ-TY5tD9mZIVQpRojGJKPf36HXYYx9tmeIVAwzKfVE7W0oF0NKEZrXYQg2U265gZlyM5Jl-Nvb8V_Rl6AysL8BUi71a4hvev4v9wgQrKH0</recordid><startdate>20130301</startdate><enddate>20130301</enddate><creator>Tanner, S M</creator><creator>Staley, E M</creator><creator>Lorenz, R G</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130301</creationdate><title>Altered generation of induced regulatory T cells in the FVB.mdr1a−/− mouse model of colitis</title><author>Tanner, S M ; Staley, E M ; Lorenz, R G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-5966f72b43348c98217c1d90d25982ae2b69ee12c6454fa499850949d0524bf43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/208/457/649</topic><topic>631/250/1619/554/1898/1271</topic><topic>692/699/249/2510/257/1389</topic><topic>Allergology</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>ATP Binding Cassette Transporter, Subfamily B - deficiency</topic><topic>ATP Binding Cassette Transporter, Subfamily B - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>CD4 Antigens - metabolism</topic><topic>Cell Movement - immunology</topic><topic>Colitis - genetics</topic><topic>Colitis - immunology</topic><topic>Disease Models, Animal</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Gastroenterology</topic><topic>Immunology</topic><topic>Interleukin-2 Receptor alpha Subunit - metabolism</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestines - immunology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>Transforming Growth Factor beta - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tanner, S M</creatorcontrib><creatorcontrib>Staley, E M</creatorcontrib><creatorcontrib>Lorenz, R G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Mucosal immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tanner, S M</au><au>Staley, E M</au><au>Lorenz, R G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered generation of induced regulatory T cells in the FVB.mdr1a−/− mouse model of colitis</atitle><jtitle>Mucosal immunology</jtitle><stitle>Mucosal Immunol</stitle><addtitle>Mucosal Immunol</addtitle><date>2013-03-01</date><risdate>2013</risdate><volume>6</volume><issue>2</issue><spage>309</spage><epage>323</epage><pages>309-323</pages><issn>1933-0219</issn><eissn>1935-3456</eissn><abstract>The FVB.
mdr1a
−/−
mouse, lacking the small molecule pump P-glycoprotein (P-gp), is a commonly used model for the study of spontaneous T cell–mediated colitis. In addition,
MDR1
polymorphisms and P-gp deficiency in humans have been linked to the development of ulcerative colitis. We now demonstrate that mice with P-gp deficiency have decreased levels of Foxp3
+
regulatory T cells (Tregs) in the intestinal lamina propria. This decrease is not due to either increased Treg apoptosis, altered Treg trafficking, or enhanced Treg plasticity to become Foxp3
+
IL-17
+
cells. Instead, P-gp deficiency appears to restrict the development of induced Treg cells (iTregs), as fewer Foxp3
+
iTregs developed from naive FVB.
mdr1a
−/−
T cells both upon transforming growth factor-β (TGF-β) treatment
in vitro
and after adoptive transfer into FVB.
rag2
−/−
recipients. Rather,
in vitro
TGF-β treatment results in a IL-17
+
CD4
+
T cell. This failure of iTregs to develop explains the decrease in Foxp3
+
Tregs in the FVB.
mdr1a
−/−
intestine, representing a need to investigate this novel disease mechanism in human inflammatory bowel disease patients with
MDR1
polymorphisms.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>22874899</pmid><doi>10.1038/mi.2012.73</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1933-0219 |
| ispartof | Mucosal immunology, 2013-03, Vol.6 (2), p.309-323 |
| issn | 1933-0219 1935-3456 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3676969 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; ProQuest Central UK/Ireland; Alma/SFX Local Collection |
| subjects | 631/208/457/649 631/250/1619/554/1898/1271 692/699/249/2510/257/1389 Allergology Animals Antibodies Apoptosis ATP Binding Cassette Transporter, Subfamily B - deficiency ATP Binding Cassette Transporter, Subfamily B - genetics Biomedical and Life Sciences Biomedicine CD4 Antigens - metabolism Cell Movement - immunology Colitis - genetics Colitis - immunology Disease Models, Animal Forkhead Transcription Factors - metabolism Gastroenterology Immunology Interleukin-2 Receptor alpha Subunit - metabolism Intestinal Mucosa - metabolism Intestines - immunology Male Mice Mice, Knockout T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism Transforming Growth Factor beta - pharmacology |
| title | Altered generation of induced regulatory T cells in the FVB.mdr1a−/− mouse model of colitis |
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