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<PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16020505</PMID><DateCompleted><Year>2005</Year><Month>11</Month><Day>30</Day></DateCompleted><DateRevised><Year>2021</Year><Month>02</Month><Day>06</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">0006-4971</ISSN><JournalIssue CitedMedium="Print"><Volume>106</Volume><Issue>9</Issue><PubDate><Year>2005</Year><Month>Nov</Month><Day>01</Day></PubDate></JournalIssue><Title>Blood</Title><ISOAbbreviation>Blood</ISOAbbreviation></Journal><ArticleTitle>Jak3 negatively regulates dendritic-cell cytokine production and survival.</ArticleTitle><Pagination><StartPage>3227</StartPage><EndPage>3233</EndPage><MedlinePgn>3227-33</MedlinePgn></Pagination><Abstract><AbstractText>Cytokines are critical in regulating the development and function of diverse cells. Janus kinase 3 (Jak3) is a tyrosine kinase expressed in hematopoietic cells that associates with the common gamma chain (gammac) and is required for signaling for a family of cytokines including interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21; deficiency of either Jak3 or gammac results in severe combined immunodeficiency (SCID). While Jak3 is essential for lymphoid-cell development, the potential roles for Jak3 in regulating dendritic cells (DCs) were unclear. Herein, we show that although CD8+CD11c+ splenic DCs are absent in Jak3-/- mice, bone marrow-derived DCs developed normally in vitro from Jak3-/- precursor cells. In fact, the survival of Jak3-/- DCs was enhanced, and they expressed lower levels of proapoptotic proteins. Jak3-/- DCs exhibited normal antigen uptake and up-regulation of costimulatory molecules. However, Jak3-/- DCs produced more IL-12 and IL-10 in response to Toll-like receptor ligands, which correlated with enhanced T helper 1 (Th1) differentiation in vivo. In summary, Jak3 is not essential for DC development but unexpectedly appears to be an important negative regulator. These results may be relevant clinically for patients with SCID who have undergone hematopoietic stem cell transplantation and for patients who might be treated with a Jak3 inhibitor.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Yamaoka</LastName><ForeName>Kunihiro</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health, Bldg 10, 9N256, 10 Center Dr, Bethesda, MD 20892-1820, USA. yamaokak@mail.nih.gov</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Min</LastName><ForeName>Booki</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Yong-Jie</ForeName><Initials>YJ</Initials></Author><Author ValidYN="Y"><LastName>Paul</LastName><ForeName>William E</ForeName><Initials>WE</Initials></Author><Author ValidYN="Y"><LastName>O'shea</LastName><ForeName>John J</ForeName><Initials>JJ</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2005</Year><Month>07</Month><Day>14</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Blood</MedlineTA><NlmUniqueID>7603509</NlmUniqueID><ISSNLinking>0006-4971</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>130068-27-8</RegistryNumber><NameOfSubstance UI="D016753">Interleukin-10</NameOfSubstance></Chemical><Chemical><RegistryNumber>187348-17-0</RegistryNumber><NameOfSubstance UI="D018664">Interleukin-12</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.1</RegistryNumber><NameOfSubstance UI="D011505">Protein-Tyrosine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.2</RegistryNumber><NameOfSubstance UI="C507935">Jak3 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.10.2</RegistryNumber><NameOfSubstance UI="D053616">Janus Kinase 3</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001853" MajorTopicYN="N">Bone Marrow</DescriptorName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002454" MajorTopicYN="N">Cell Differentiation</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003713" MajorTopicYN="N">Dendritic Cells</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016753" MajorTopicYN="N">Interleukin-10</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018664" MajorTopicYN="N">Interleukin-12</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053616" MajorTopicYN="N">Janus Kinase 3</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011505" MajorTopicYN="N">Protein-Tyrosine Kinases</DescriptorName><QualifierName UI="Q000172" MajorTopicYN="N">deficiency</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013154" MajorTopicYN="N">Spleen</DescriptorName><QualifierName UI="Q000002" MajorTopicYN="N">abnormalities</QualifierName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018417" MajorTopicYN="N">Th1 Cells</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2005</Year><Month>7</Month><Day>16</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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