Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα
Myelofibrosis (MF), including primary myelofibrosis, post-essential thrombocythemia MF, and post-polycythemia vera MF, has been reported to be associated with autoimmune phenomena. IMiDs have been reported to be effective in some patients with MF, presumably for their immune-modulator effects. We th...
Gespeichert in:
| Veröffentlicht in: | PloS one 2015-03, Vol.10 (3), p.e0116723-e0116723 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0116723 |
|---|---|
| container_issue | 3 |
| container_start_page | e0116723 |
| container_title | PloS one |
| container_volume | 10 |
| creator | Wang, Jen C Sindhu, Hemant Chen, Chi Kundra, Ajay Kafeel, Muhammad I Wong, Ching Lichter, Stephen |
| description | Myelofibrosis (MF), including primary myelofibrosis, post-essential thrombocythemia MF, and post-polycythemia vera MF, has been reported to be associated with autoimmune phenomena. IMiDs have been reported to be effective in some patients with MF, presumably for their immune-modulator effects. We therefore sought to elucidate the immune derangements in patients with MF. We found no differences in T regulatory cells (Treg) and T helper 17 (Th17) cells in MF patients and normal healthy controls. However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls. Our studies with MF patients further revealed that Treg cells were the predominant cells producing sIL2Rα. sIL2Rα and IL2 complex induced the formation of Treg cells but not the formation of Th1 or Th17 cells. sIL2Rα induced CD8+ T cell proliferation in the presence of Treg cells. Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells. Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms. All these findings suggest that sIL2Rα likely plays a significant role in autoimmune phenomena seen in patients with MF. Further studies of immune derangement may elucidate the mechanism of IMiD, and exploration of immune modulators may prove to be important for treating myelofibrosis. |
| doi_str_mv | 10.1371/journal.pone.0116723 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1664930485</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_dd01d285c2304085ad6f4febfe83d75b</doaj_id><sourcerecordid>3631002571</sourcerecordid><originalsourceid>FETCH-LOGICAL-c526t-c8499218499684f630c793cec786ec3da622fc2f4761e9e054d944894d4200ee3</originalsourceid><addsrcrecordid>eNptUt2KEzEYHURx19U3EA1448W25m8yiReCLP4UCoJUvAxp8qVNmZnUZEbZx_JFfCbTdnbZFW-Sj-Sck_N9OVX1nOA5YQ15s4tj6k0738ce5pgQ0VD2oDonitGZoJg9vFOfVU9y3mFcMynE4-qM1o1igrLz6vui68YekINk-g100A8ZhR7tzRCO9a8wbFF3DW30YZ1iDvktGraAUmwBRY9WCTaXaLUlzSUyvUN5saRf__x-Wj3yps3wbNovqm8fP6yuPs-WXz4trt4vZ7amYphZyZWi5LAKyb1g2BZnFmwjBVjmjKDUW-p5IwgowDV3inOpuOMUYwB2Ub086e7bmPU0k6yJEFwxzGVdEIsTwkWz0_sUOpOudTRBHw9i2miThmBb0M5h4qisLS1ULGvjhOce1h4kc029LlrvptfGdQfOlgkl094TvX_Th63exJ-aMyGFwkXg9SSQ4o8R8qC7kC20rekhjkffgiquCC_QV_9A_98dP6Fs-ZucwN-aIVgfcnLD0oec6CknhfbibiO3pJtgsL8cjrrX</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1664930485</pqid></control><display><type>article</type><title>Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Wang, Jen C ; Sindhu, Hemant ; Chen, Chi ; Kundra, Ajay ; Kafeel, Muhammad I ; Wong, Ching ; Lichter, Stephen</creator><creatorcontrib>Wang, Jen C ; Sindhu, Hemant ; Chen, Chi ; Kundra, Ajay ; Kafeel, Muhammad I ; Wong, Ching ; Lichter, Stephen</creatorcontrib><description>Myelofibrosis (MF), including primary myelofibrosis, post-essential thrombocythemia MF, and post-polycythemia vera MF, has been reported to be associated with autoimmune phenomena. IMiDs have been reported to be effective in some patients with MF, presumably for their immune-modulator effects. We therefore sought to elucidate the immune derangements in patients with MF. We found no differences in T regulatory cells (Treg) and T helper 17 (Th17) cells in MF patients and normal healthy controls. However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls. Our studies with MF patients further revealed that Treg cells were the predominant cells producing sIL2Rα. sIL2Rα and IL2 complex induced the formation of Treg cells but not the formation of Th1 or Th17 cells. sIL2Rα induced CD8+ T cell proliferation in the presence of Treg cells. Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells. Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms. All these findings suggest that sIL2Rα likely plays a significant role in autoimmune phenomena seen in patients with MF. Further studies of immune derangement may elucidate the mechanism of IMiD, and exploration of immune modulators may prove to be important for treating myelofibrosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0116723</identifier><identifier>PMID: 25793623</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Autoimmune diseases ; Autoimmunity ; Blood cancer ; Bone marrow ; Case-Control Studies ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Cell Differentiation ; Cell Proliferation ; Cytokines ; Female ; Helper cells ; Hematology ; Hospitals ; Humans ; Immunomodulation ; Immunoregulation ; Interleukin ; Interleukin 2 ; Interleukin-2 Receptor alpha Subunit - blood ; Interleukin-2 Receptor alpha Subunit - metabolism ; Leukemia ; Leukocytes (neutrophilic) ; Lupus ; Lymphocytes T ; Lymphoma ; Lymphomas ; Male ; Melanoma ; Middle Aged ; Modulators ; Monocytes ; Monocytes - drug effects ; Multiple sclerosis ; Myelofibrosis ; Neutrophils - drug effects ; Oncology ; Ovarian cancer ; Patients ; Polycythemia ; Polycythemia vera ; Primary Myelofibrosis - blood ; Primary Myelofibrosis - immunology ; Pyrazoles - pharmacology ; Serology ; Solubility ; Studies ; T cell receptors ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; Th17 Cells - drug effects ; Th17 Cells - immunology ; Tumors</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0116723-e0116723</ispartof><rights>2015 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Wang et al 2015 Wang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-c8499218499684f630c793cec786ec3da622fc2f4761e9e054d944894d4200ee3</citedby><cites>FETCH-LOGICAL-c526t-c8499218499684f630c793cec786ec3da622fc2f4761e9e054d944894d4200ee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368690/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368690/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25793623$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Jen C</creatorcontrib><creatorcontrib>Sindhu, Hemant</creatorcontrib><creatorcontrib>Chen, Chi</creatorcontrib><creatorcontrib>Kundra, Ajay</creatorcontrib><creatorcontrib>Kafeel, Muhammad I</creatorcontrib><creatorcontrib>Wong, Ching</creatorcontrib><creatorcontrib>Lichter, Stephen</creatorcontrib><title>Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Myelofibrosis (MF), including primary myelofibrosis, post-essential thrombocythemia MF, and post-polycythemia vera MF, has been reported to be associated with autoimmune phenomena. IMiDs have been reported to be effective in some patients with MF, presumably for their immune-modulator effects. We therefore sought to elucidate the immune derangements in patients with MF. We found no differences in T regulatory cells (Treg) and T helper 17 (Th17) cells in MF patients and normal healthy controls. However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls. Our studies with MF patients further revealed that Treg cells were the predominant cells producing sIL2Rα. sIL2Rα and IL2 complex induced the formation of Treg cells but not the formation of Th1 or Th17 cells. sIL2Rα induced CD8+ T cell proliferation in the presence of Treg cells. Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells. Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms. All these findings suggest that sIL2Rα likely plays a significant role in autoimmune phenomena seen in patients with MF. Further studies of immune derangement may elucidate the mechanism of IMiD, and exploration of immune modulators may prove to be important for treating myelofibrosis.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Autoimmune diseases</subject><subject>Autoimmunity</subject><subject>Blood cancer</subject><subject>Bone marrow</subject><subject>Case-Control Studies</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell Differentiation</subject><subject>Cell Proliferation</subject><subject>Cytokines</subject><subject>Female</subject><subject>Helper cells</subject><subject>Hematology</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunomodulation</subject><subject>Immunoregulation</subject><subject>Interleukin</subject><subject>Interleukin 2</subject><subject>Interleukin-2 Receptor alpha Subunit - blood</subject><subject>Interleukin-2 Receptor alpha Subunit - metabolism</subject><subject>Leukemia</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lupus</subject><subject>Lymphocytes T</subject><subject>Lymphoma</subject><subject>Lymphomas</subject><subject>Male</subject><subject>Melanoma</subject><subject>Middle Aged</subject><subject>Modulators</subject><subject>Monocytes</subject><subject>Monocytes - drug effects</subject><subject>Multiple sclerosis</subject><subject>Myelofibrosis</subject><subject>Neutrophils - drug effects</subject><subject>Oncology</subject><subject>Ovarian cancer</subject><subject>Patients</subject><subject>Polycythemia</subject><subject>Polycythemia vera</subject><subject>Primary Myelofibrosis - blood</subject><subject>Primary Myelofibrosis - immunology</subject><subject>Pyrazoles - pharmacology</subject><subject>Serology</subject><subject>Solubility</subject><subject>Studies</subject><subject>T cell receptors</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Th17 Cells - drug effects</subject><subject>Th17 Cells - immunology</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUt2KEzEYHURx19U3EA1448W25m8yiReCLP4UCoJUvAxp8qVNmZnUZEbZx_JFfCbTdnbZFW-Sj-Sck_N9OVX1nOA5YQ15s4tj6k0738ce5pgQ0VD2oDonitGZoJg9vFOfVU9y3mFcMynE4-qM1o1igrLz6vui68YekINk-g100A8ZhR7tzRCO9a8wbFF3DW30YZ1iDvktGraAUmwBRY9WCTaXaLUlzSUyvUN5saRf__x-Wj3yps3wbNovqm8fP6yuPs-WXz4trt4vZ7amYphZyZWi5LAKyb1g2BZnFmwjBVjmjKDUW-p5IwgowDV3inOpuOMUYwB2Ub086e7bmPU0k6yJEFwxzGVdEIsTwkWz0_sUOpOudTRBHw9i2miThmBb0M5h4qisLS1ULGvjhOce1h4kc029LlrvptfGdQfOlgkl094TvX_Th63exJ-aMyGFwkXg9SSQ4o8R8qC7kC20rekhjkffgiquCC_QV_9A_98dP6Fs-ZucwN-aIVgfcnLD0oec6CknhfbibiO3pJtgsL8cjrrX</recordid><startdate>20150320</startdate><enddate>20150320</enddate><creator>Wang, Jen C</creator><creator>Sindhu, Hemant</creator><creator>Chen, Chi</creator><creator>Kundra, Ajay</creator><creator>Kafeel, Muhammad I</creator><creator>Wong, Ching</creator><creator>Lichter, Stephen</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150320</creationdate><title>Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα</title><author>Wang, Jen C ; Sindhu, Hemant ; Chen, Chi ; Kundra, Ajay ; Kafeel, Muhammad I ; Wong, Ching ; Lichter, Stephen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-c8499218499684f630c793cec786ec3da622fc2f4761e9e054d944894d4200ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Autoimmune diseases</topic><topic>Autoimmunity</topic><topic>Blood cancer</topic><topic>Bone marrow</topic><topic>Case-Control Studies</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell Differentiation</topic><topic>Cell Proliferation</topic><topic>Cytokines</topic><topic>Female</topic><topic>Helper cells</topic><topic>Hematology</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunomodulation</topic><topic>Immunoregulation</topic><topic>Interleukin</topic><topic>Interleukin 2</topic><topic>Interleukin-2 Receptor alpha Subunit - blood</topic><topic>Interleukin-2 Receptor alpha Subunit - metabolism</topic><topic>Leukemia</topic><topic>Leukocytes (neutrophilic)</topic><topic>Lupus</topic><topic>Lymphocytes T</topic><topic>Lymphoma</topic><topic>Lymphomas</topic><topic>Male</topic><topic>Melanoma</topic><topic>Middle Aged</topic><topic>Modulators</topic><topic>Monocytes</topic><topic>Monocytes - drug effects</topic><topic>Multiple sclerosis</topic><topic>Myelofibrosis</topic><topic>Neutrophils - drug effects</topic><topic>Oncology</topic><topic>Ovarian cancer</topic><topic>Patients</topic><topic>Polycythemia</topic><topic>Polycythemia vera</topic><topic>Primary Myelofibrosis - blood</topic><topic>Primary Myelofibrosis - immunology</topic><topic>Pyrazoles - pharmacology</topic><topic>Serology</topic><topic>Solubility</topic><topic>Studies</topic><topic>T cell receptors</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Th17 Cells - drug effects</topic><topic>Th17 Cells - immunology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Jen C</creatorcontrib><creatorcontrib>Sindhu, Hemant</creatorcontrib><creatorcontrib>Chen, Chi</creatorcontrib><creatorcontrib>Kundra, Ajay</creatorcontrib><creatorcontrib>Kafeel, Muhammad I</creatorcontrib><creatorcontrib>Wong, Ching</creatorcontrib><creatorcontrib>Lichter, Stephen</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</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>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content 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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Jen C</au><au>Sindhu, Hemant</au><au>Chen, Chi</au><au>Kundra, Ajay</au><au>Kafeel, Muhammad I</au><au>Wong, Ching</au><au>Lichter, Stephen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-03-20</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><spage>e0116723</spage><epage>e0116723</epage><pages>e0116723-e0116723</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Myelofibrosis (MF), including primary myelofibrosis, post-essential thrombocythemia MF, and post-polycythemia vera MF, has been reported to be associated with autoimmune phenomena. IMiDs have been reported to be effective in some patients with MF, presumably for their immune-modulator effects. We therefore sought to elucidate the immune derangements in patients with MF. We found no differences in T regulatory cells (Treg) and T helper 17 (Th17) cells in MF patients and normal healthy controls. However, we found significantly elevated soluble interleukin 2 alpha (sIL2Rα) in MF patients compared to those with other myeloproliferative neoplasm diseases and normal healthy controls. Our studies with MF patients further revealed that Treg cells were the predominant cells producing sIL2Rα. sIL2Rα and IL2 complex induced the formation of Treg cells but not the formation of Th1 or Th17 cells. sIL2Rα induced CD8+ T cell proliferation in the presence of Treg cells. Monocytes or neutrophils had no effect on the production of sIL2Rα by Treg cells. Furthermore, we found plasma sIL2Rα levels were correlated to the auto-immune serology in MPN patients and ruxolitinib significantly inhibits the sIL2Rα production by the Treg cells in MF patients which may explain the effects of ruxolitinib on the relief of constitutional symptoms. All these findings suggest that sIL2Rα likely plays a significant role in autoimmune phenomena seen in patients with MF. Further studies of immune derangement may elucidate the mechanism of IMiD, and exploration of immune modulators may prove to be important for treating myelofibrosis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25793623</pmid><doi>10.1371/journal.pone.0116723</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-03, Vol.10 (3), p.e0116723-e0116723 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1664930485 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Aged Aged, 80 and over Autoimmune diseases Autoimmunity Blood cancer Bone marrow Case-Control Studies CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell Differentiation Cell Proliferation Cytokines Female Helper cells Hematology Hospitals Humans Immunomodulation Immunoregulation Interleukin Interleukin 2 Interleukin-2 Receptor alpha Subunit - blood Interleukin-2 Receptor alpha Subunit - metabolism Leukemia Leukocytes (neutrophilic) Lupus Lymphocytes T Lymphoma Lymphomas Male Melanoma Middle Aged Modulators Monocytes Monocytes - drug effects Multiple sclerosis Myelofibrosis Neutrophils - drug effects Oncology Ovarian cancer Patients Polycythemia Polycythemia vera Primary Myelofibrosis - blood Primary Myelofibrosis - immunology Pyrazoles - pharmacology Serology Solubility Studies T cell receptors T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology Th17 Cells - drug effects Th17 Cells - immunology Tumors |
| title | Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T09%3A47%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Immune%20derangements%20in%20patients%20with%20myelofibrosis:%20the%20role%20of%20Treg,%20Th17,%20and%20sIL2R%CE%B1&rft.jtitle=PloS%20one&rft.au=Wang,%20Jen%20C&rft.date=2015-03-20&rft.volume=10&rft.issue=3&rft.spage=e0116723&rft.epage=e0116723&rft.pages=e0116723-e0116723&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0116723&rft_dat=%3Cproquest_plos_%3E3631002571%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1664930485&rft_id=info:pmid/25793623&rft_doaj_id=oai_doaj_org_article_dd01d285c2304085ad6f4febfe83d75b&rfr_iscdi=true |