Advances in Experimental Medicine and Biology 841 Bing Sun Editor T Helper Cell Differentiation and Their Function Advances in Experimental Medicine and Biology Volume 841 Series editors Irun R. Cohen, Rehovot, Israel N.S. Abel Lajtha, Orangeburg, USA Rodolfo Paoletti, Milan, Italy John D. Lambris, Philadelphia, USA More information about this series at http://www.springer.com/series/5584 Bing Sun Editor T Helper Cell Differentiation and Their Function 123 Editor Bing Sun Instituteof Biochemistryand Cell Biology ChineseAcademy ofSciences Shanghai China ISSN 0065-2598 ISSN 2214-8019 (electronic) ISBN 978-94-017-9486-2 ISBN 978-94-017-9487-9 (eBook) DOI 10.1007/978-94-017-9487-9 LibraryofCongressControlNumber:2014951155 SpringerDordrechtHeidelbergNewYorkLondon ©SpringerScience+BusinessMediaDordrecht2014 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodology now known or hereafter developed. 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While the advice and information in this book are believed to be true and accurate at the date of publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with respecttothematerialcontainedherein. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface ThisbookfocusesonthedifferentiationandregulationofvarioussubsetsofCD4+ T cells. It also covers CD4+ T cell subset plasticity and CD4+ T cell function in physiological and diseased states. Where the classic T cell model describes that every subset or subpopulation of T cells develops by producing its own unique cytokinesandmasterregulators,morerecentresearchhasshownthatthetruthmay beabitmorecomplicated.WithnewtechnologiessuchasChIP-seq,RNA-seq,and data-based analysis, potential transcript factors and binding cites have been iden- tifiedindifferentTcellsubsetsanddifferentiationstages.Theseresultssuggestthat Tcelldifferentiationisnotalinearprocessfromstarttofinishthatcanbeswitched “on” and “off,” but is the result of complex molecular signaling cascades, subtly controlledbyavarietyofmasterregulators.Additionally,epigeneticregulation,the modificationofDNAorhistones,mighthelptodecideTcellfatebyfacilitatingor blocking the binding of transcript factors. While correct and moderate stimulation willleadtopreciseTcellresponses,incorrectsignalscausedysfunctionslikeauto- immune diseases and allergies. As CD4+ T cells play the key role in our adaptive immunesystem,examiningchemokinereceptorinterferencebysmallmoleculesor antibodies represents a new approach to disease treatment. This book provides researchers, graduate students, and clinic practitioners with a cutting-edge and comprehensive summary of research on CD4+ T cells and their potential applica- tions in the clinic. I sincerely thank all the chapter authors for their great contri- butiontothebook.IalsothankQiaoshiLian,HaiyanZhou,andWenjingXuanfor their coordination and help. v Contents 1 Overview of Orchestration of CD4+ T Cell Subsets in Immune Responses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bing Sun and Yuan Zhang 2 Th1/Th2 Cell Differentiation and Molecular Signals. . . . . . . . . . . 15 Yuan Zhang, Yaguang Zhang, Wangpeng Gu and Bing Sun 3 Th1/Th2 Cell’s Function in Immune System . . . . . . . . . . . . . . . . 45 Yuan Zhang, Yaguang Zhang, Wangpeng Gu, Lan He and Bing Sun 4 Regulatory T-Cell Differentiation and Their Function in Immune Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Miranda Piccioni, Zuojia Chen, Andy Tsun and Bin Li 5 Th17 Differentiation and Their Pro-inflammation Function. . . . . . 99 Xinyang Song, Hanchao Gao and Youcun Qian 6 Tfh Cell Differentiation and Their Function in Promoting B-Cell Responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 Hai Qi, Xin Chen, Coco Chu, Dan Liu, Weiwei Ma, Yifeng Wang, Longyan Wu, Hu Yan and Jiacong Yan 7 Differentiation, Regulation and Function of Th9 Cells . . . . . . . . . 181 Lei Jia and Changyou Wu 8 The Biology and Functions of Th22 Cells. . . . . . . . . . . . . . . . . . . 209 Lei Jia and Changyou Wu vii Contributors Zuojia Chen Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China XinChen LaboratoryofDynamicImmunobiology,SchoolofMedicine,Schoolof Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, People’s Republic of China Coco Chu Laboratory of Dynamic Immunobiology, School of Medicine, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, People’s Republic of China Hanchao Gao The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China Wangpeng Gu State Key Laboratory of Cell Biology, Institute of Biochemistry andCellBiology,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyof Sciences, Shanghai, China Lan He State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China Lei Jia Key Laboratory of Tropical Disease Control Research of Ministry of Education, Zhongshan School of Medicine, Institute of Immunology, Sun Yat-Sen University, Guangzhou, China Bin Li Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China ix x Contributors DanLiu LaboratoryofDynamicImmunobiology,SchoolofMedicine,Schoolof Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, People’s Republic of China WeiweiMa LaboratoryofDynamicImmunobiology,SchoolofMedicine,School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, People’s Republic of China Miranda Piccioni Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China Hai Qi Laboratory of Dynamic Immunobiology, School of Medicine, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, People’s Republic of China Youcun Qian The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China Xinyang Song The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China BingSun StateKeyLaboratoryofCellBiology,InstituteofBiochemistryandCell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China Andy Tsun Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Institutes for Biological Sciences,ChineseAcademyofSciences,Shanghai,China;NewDrugandCellLine Development, Department of Process Development, Innovent Biologics Inc, Suzhou, China Yifeng Wang Laboratory of Dynamic Immunobiology, School of Medicine, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, People’s Republic of China ChangyouWu KeyLaboratoryofTropicalDiseaseControlResearchofMinistry of Education, Zhongshan School of Medicine, Institute of Immunology, Sun Yat-Sen University, Guangzhou, China Longyan Wu Laboratory of Dynamic Immunobiology, School of Medicine, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, People’s Republic of China Jiacong Yan Laboratory of Dynamic Immunobiology, School of Medicine, School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, People’s Republic of China Contributors xi HuYan LaboratoryofDynamicImmunobiology,SchoolofMedicine,Schoolof Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, People’s Republic of China Yaguang Zhang State Key Laboratory of Cell Biology, Instituteof Biochemistry andCellBiology,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyof Sciences, Shanghai, China YuanZhang StateKeyLaboratoryofCellBiology,InstituteofBiochemistryand Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China