The anti‐inflammatory effects of 1,25‐dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin‐mediated T lymphocyte homing
The fat soluble vitamin D3 metabolite 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3], and its nuclear receptor play an important role in regulating immune responses. While 1,25(OH)2D3 is known to inhibit transcription of cytokine genes that are required for Th1 differentiation or are products of differentia...
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| Veröffentlicht in: | European journal of immunology 2004-04, Vol.34 (4), p.1068-1076 |
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| container_title | European journal of immunology |
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| creator | Topilski, Ian Flaishon, Liat Naveh, Yaron Harmelin, Alon Levo, Yoram Shachar, Idit |
| description | The fat soluble vitamin D3 metabolite 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3], and its nuclear receptor play an important role in regulating immune responses. While 1,25(OH)2D3 is known to inhibit transcription of cytokine genes that are required for Th1 differentiation or are products of differentiated Th1 cells, its role in regulating differentiation of Th2 cells is less clear. In this study, we show that 1,25(OH)2D3 has anti‐inflammatory effects in an in vivo Th2‐dependent asthma model. In addition, we demonstrate that 1,25(OH)2D3 down‐regulates the cytoskeleton rearrangement required for promoting integrin‐mediated adhesion of naive and effector CD4+ T cells. Finally, 1,25(OH)2D3 inhibits chemokine‐induced migration of naive cells and their homing to the lymph nodes. Thus, in addition to its regulation of cytokine transcription, 1,25(OH)2D3 regulates migration of cells and thus controls the skewing of various Th subsets in the secondary lymphoid organs and inhibits Th function at sites of inflammation. |
| doi_str_mv | 10.1002/eji.200324532 |
| format | Article |
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While 1,25(OH)2D3 is known to inhibit transcription of cytokine genes that are required for Th1 differentiation or are products of differentiated Th1 cells, its role in regulating differentiation of Th2 cells is less clear. In this study, we show that 1,25(OH)2D3 has anti‐inflammatory effects in an in vivo Th2‐dependent asthma model. In addition, we demonstrate that 1,25(OH)2D3 down‐regulates the cytoskeleton rearrangement required for promoting integrin‐mediated adhesion of naive and effector CD4+ T cells. Finally, 1,25(OH)2D3 inhibits chemokine‐induced migration of naive cells and their homing to the lymph nodes. Thus, in addition to its regulation of cytokine transcription, 1,25(OH)2D3 regulates migration of cells and thus controls the skewing of various Th subsets in the secondary lymphoid organs and inhibits Th function at sites of inflammation.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.200324532</identifier><identifier>PMID: 15048717</identifier><language>eng</language><publisher>Weinheim: WILEY‐VCH Verlag</publisher><subject>Animals ; Asthma ; Asthma - chemically induced ; Asthma - immunology ; Asthma - physiopathology ; Bronchoalveolar Lavage Fluid - chemistry ; Calcitriol - pharmacology ; CD4 T cells ; Cell Differentiation - immunology ; Cell Movement - drug effects ; Cell Movement - immunology ; Cytoskeleton - drug effects ; Cytoskeleton - immunology ; Cytoskeleton rearrangement ; Disease Models, Animal ; Inflammation - immunology ; Integrins - immunology ; Interleukin-4 - analysis ; Lung - immunology ; Lung - pathology ; Mice ; Migration ; Ovalbumin - immunology ; Ovalbumin - toxicity ; Th2 cells ; Th2 Cells - immunology ; Vitamin D</subject><ispartof>European journal of immunology, 2004-04, Vol.34 (4), p.1068-1076</ispartof><rights>Copyright © 2004 WILEY‐VCH Verlag GmbH & Co. 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While 1,25(OH)2D3 is known to inhibit transcription of cytokine genes that are required for Th1 differentiation or are products of differentiated Th1 cells, its role in regulating differentiation of Th2 cells is less clear. In this study, we show that 1,25(OH)2D3 has anti‐inflammatory effects in an in vivo Th2‐dependent asthma model. In addition, we demonstrate that 1,25(OH)2D3 down‐regulates the cytoskeleton rearrangement required for promoting integrin‐mediated adhesion of naive and effector CD4+ T cells. Finally, 1,25(OH)2D3 inhibits chemokine‐induced migration of naive cells and their homing to the lymph nodes. Thus, in addition to its regulation of cytokine transcription, 1,25(OH)2D3 regulates migration of cells and thus controls the skewing of various Th subsets in the secondary lymphoid organs and inhibits Th function at sites of inflammation.</description><subject>Animals</subject><subject>Asthma</subject><subject>Asthma - chemically induced</subject><subject>Asthma - immunology</subject><subject>Asthma - physiopathology</subject><subject>Bronchoalveolar Lavage Fluid - chemistry</subject><subject>Calcitriol - pharmacology</subject><subject>CD4 T cells</subject><subject>Cell Differentiation - immunology</subject><subject>Cell Movement - drug effects</subject><subject>Cell Movement - immunology</subject><subject>Cytoskeleton - drug effects</subject><subject>Cytoskeleton - immunology</subject><subject>Cytoskeleton rearrangement</subject><subject>Disease Models, Animal</subject><subject>Inflammation - immunology</subject><subject>Integrins - immunology</subject><subject>Interleukin-4 - analysis</subject><subject>Lung - immunology</subject><subject>Lung - pathology</subject><subject>Mice</subject><subject>Migration</subject><subject>Ovalbumin - immunology</subject><subject>Ovalbumin - toxicity</subject><subject>Th2 cells</subject><subject>Th2 Cells - immunology</subject><subject>Vitamin D</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFO3DAQhi1UBAvlyLXyqSdCx44dJ8eKQkuFxGV7jpxkTIySeGt7t-TGI_AAPF2fBK92VW6VD5bHn77RzE_IOYNLBsC_4KO95AA5FzLnB2TBJGeZYIJ9IAsAJjJelXBMTkJ4BICqkNUROWYSRKmYWpDXZY9UT9H-fX6xkxn0OOro_EzRGGxjoM5QdsFl-u5sP3fePc0bG_VoJ_otp26iy57TFoch0FTa2I2j2iPt1rh9r7SPNDoaU5fWTdG7YWu0U8QHb6dkHbGzOmJHl3SYx1Xv2jki7V1q8PCRHBo9BDzb36fk18318upHdnf__fbq613WClA8a0rQKEU6BRSMKamEbosib4Rg3IDppKlQys5wIQRIUZWq0RIKqRomSg75Kfm88668-73GEOvRhu1MekK3DjVTVS7zXCUw24GtdyF4NPXK21H7uWZQb-OoUxz1vzgS_2kvXjdp0Hd6v_8EqB3wxw44_99WX_-8fVe_AcsSmKw</recordid><startdate>200404</startdate><enddate>200404</enddate><creator>Topilski, Ian</creator><creator>Flaishon, Liat</creator><creator>Naveh, Yaron</creator><creator>Harmelin, Alon</creator><creator>Levo, Yoram</creator><creator>Shachar, Idit</creator><general>WILEY‐VCH Verlag</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>7T5</scope><scope>H94</scope></search><sort><creationdate>200404</creationdate><title>The anti‐inflammatory effects of 1,25‐dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin‐mediated T lymphocyte homing</title><author>Topilski, Ian ; Flaishon, Liat ; Naveh, Yaron ; Harmelin, Alon ; Levo, Yoram ; Shachar, Idit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4072-b80ae54545606117574ac663b4412f0fd5f9e55df2444054987ba50657b148203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Asthma</topic><topic>Asthma - chemically induced</topic><topic>Asthma - immunology</topic><topic>Asthma - physiopathology</topic><topic>Bronchoalveolar Lavage Fluid - chemistry</topic><topic>Calcitriol - pharmacology</topic><topic>CD4 T cells</topic><topic>Cell Differentiation - immunology</topic><topic>Cell Movement - drug effects</topic><topic>Cell Movement - immunology</topic><topic>Cytoskeleton - drug effects</topic><topic>Cytoskeleton - immunology</topic><topic>Cytoskeleton rearrangement</topic><topic>Disease Models, Animal</topic><topic>Inflammation - immunology</topic><topic>Integrins - immunology</topic><topic>Interleukin-4 - analysis</topic><topic>Lung - immunology</topic><topic>Lung - pathology</topic><topic>Mice</topic><topic>Migration</topic><topic>Ovalbumin - immunology</topic><topic>Ovalbumin - toxicity</topic><topic>Th2 cells</topic><topic>Th2 Cells - immunology</topic><topic>Vitamin D</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Topilski, Ian</creatorcontrib><creatorcontrib>Flaishon, Liat</creatorcontrib><creatorcontrib>Naveh, Yaron</creatorcontrib><creatorcontrib>Harmelin, Alon</creatorcontrib><creatorcontrib>Levo, Yoram</creatorcontrib><creatorcontrib>Shachar, Idit</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>European journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Topilski, Ian</au><au>Flaishon, Liat</au><au>Naveh, Yaron</au><au>Harmelin, Alon</au><au>Levo, Yoram</au><au>Shachar, Idit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The anti‐inflammatory effects of 1,25‐dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin‐mediated T lymphocyte homing</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2004-04</date><risdate>2004</risdate><volume>34</volume><issue>4</issue><spage>1068</spage><epage>1076</epage><pages>1068-1076</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><abstract>The fat soluble vitamin D3 metabolite 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3], and its nuclear receptor play an important role in regulating immune responses. While 1,25(OH)2D3 is known to inhibit transcription of cytokine genes that are required for Th1 differentiation or are products of differentiated Th1 cells, its role in regulating differentiation of Th2 cells is less clear. In this study, we show that 1,25(OH)2D3 has anti‐inflammatory effects in an in vivo Th2‐dependent asthma model. In addition, we demonstrate that 1,25(OH)2D3 down‐regulates the cytoskeleton rearrangement required for promoting integrin‐mediated adhesion of naive and effector CD4+ T cells. Finally, 1,25(OH)2D3 inhibits chemokine‐induced migration of naive cells and their homing to the lymph nodes. 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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Wiley Online Library Free Content; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Asthma Asthma - chemically induced Asthma - immunology Asthma - physiopathology Bronchoalveolar Lavage Fluid - chemistry Calcitriol - pharmacology CD4 T cells Cell Differentiation - immunology Cell Movement - drug effects Cell Movement - immunology Cytoskeleton - drug effects Cytoskeleton - immunology Cytoskeleton rearrangement Disease Models, Animal Inflammation - immunology Integrins - immunology Interleukin-4 - analysis Lung - immunology Lung - pathology Mice Migration Ovalbumin - immunology Ovalbumin - toxicity Th2 cells Th2 Cells - immunology Vitamin D |
| title | The anti‐inflammatory effects of 1,25‐dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin‐mediated T lymphocyte homing |
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