Innate lymphoid cells: emerging insights in development, lineage relationships, and function.

Innate lymphoid cells (ILCs) are immune cells that lack a specific antigen receptor yet can produce an array of effector cytokines that in variety match that of T helper cell subsets. ILCs function in lymphoid organogenesis, tissue remodeling, antimicrobial immunity, and inflammation, particularly at barrier surfaces. Their ability to promptly respond to insults inflicted by stress-causing microbes strongly suggests that ILCs are critical in first-line immunological defenses. Here, we review current data on developmental requirements, lineage relationships, and effector functions of two families of ILCs: (a) Rorγt-expressing cells involved in lymphoid tissue formation, mucosal immunity, and inflammation and (b) type 2 ILCs that are important for helminth immunity. We also discuss the potential roles of ILCs in the pathology of immune-mediated inflammatory and infectious diseases including allergy.

[1]  E. Hobeika,et al.  Natural Aryl Hydrocarbon Receptor Ligands Control Organogenesis of Intestinal Lymphoid Follicles , 2011, Science.

[2]  David Artis,et al.  Cutting Edge: Natural Helper Cells Derive from Lymphoid Progenitors , 2011, The Journal of Immunology.

[3]  C. Garlanda,et al.  AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch , 2011, Nature Immunology.

[4]  David Artis,et al.  Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus , 2011, Nature Immunology.

[5]  Hergen Spits,et al.  Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161 , 2011, Nature Immunology.

[6]  A. Cumano,et al.  Notch signaling is necessary for adult, but not fetal, development of RORγt+ innate lymphoid cells , 2011, Nature Immunology.

[7]  Nicola A Hanania,et al.  Lebrikizumab treatment in adults with asthma. , 2011, The New England journal of medicine.

[8]  S. Nedospasov,et al.  Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge. , 2011, Cell host & microbe.

[9]  H. Spits Another armament in gut immunity: lymphotoxin-mediated crosstalk between innate lymphoid and dendritic cells. , 2011, Cell host & microbe.

[10]  J. Renauld,et al.  Identity, regulation and in vivo function of gut NKp46+RORγt+ and NKp46+RORγt− lymphoid cells , 2011, The EMBO journal.

[11]  B. Becher,et al.  IL-22 Is Produced by Innate Lymphoid Cells and Limits Inflammation in Allergic Airway Disease , 2011, PloS one.

[12]  Ya-Jen Chang,et al.  Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity , 2011, Nature Immunology.

[13]  S. Travis,et al.  IL-23–responsive innate lymphoid cells are increased in inflammatory bowel disease , 2011, The Journal of experimental medicine.

[14]  G. Anderson,et al.  CD117+CD3−CD56−OX40Lhigh cells express IL‐22 and display an LTi phenotype in human secondary lymphoid tissues , 2011, European journal of immunology.

[15]  R. Reijmers,et al.  Activation and effector functions of human RORC+ innate lymphoid cells. , 2011, Current opinion in immunology.

[16]  R. Maizels,et al.  Diversity and dialogue in immunity to helminths , 2011, Nature Reviews Immunology.

[17]  J. Kolls,et al.  The development of inducible Bronchus Associated Lymphoid Tissue (iBALT) is dependent on IL-17 , 2011, Nature Immunology.

[18]  D. Artis,et al.  Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22 , 2011, Nature Immunology.

[19]  B. Blazar,et al.  Development of IL-22-producing NK lineage cells from umbilical cord blood hematopoietic stem cells in the absence of secondary lymphoid tissue. , 2011, Blood.

[20]  M. Veldhoen,et al.  External influences on the immune system via activation of the aryl hydrocarbon receptor. , 2011, Seminars in immunology.

[21]  Hergen Spits,et al.  Quantitative events determine the differentiation and function of helper T cells , 2011, Nature Immunology.

[22]  W. Held,et al.  The function of natural killer cells: education, reminders and some good memories. , 2011, Current opinion in immunology.

[23]  J. Sirard,et al.  IL‐22 is produced by γC‐independent CD25+ CCR6+ innate murine spleen cells upon inflammatory stimuli and contributes to LPS‐induced lethality , 2011, European journal of immunology.

[24]  G. Eberl,et al.  RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota , 2011, Nature Immunology.

[25]  S. Rutz,et al.  Regulation and functions of the IL-10 family of cytokines in inflammation and disease. , 2011, Annual review of immunology.

[26]  J. D. Di Santo,et al.  Lymphotoxin‐β receptor‐independent development of intestinal IL‐22‐producing NKp46+ innate lymphoid cells , 2011, European journal of immunology.

[27]  Yoichiro Iwakura,et al.  Review Functional Specialization of Interleukin-17 Family Members , 2022 .

[28]  D. Artis,et al.  CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut. , 2011, Immunity.

[29]  M. Si-Tahar,et al.  Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORγt and LTi cells , 2011, The Journal of experimental medicine.

[30]  M. Caligiuri,et al.  Innate or Adaptive Immunity? The Example of Natural Killer Cells , 2011, Science.

[31]  M. Veldhoen,et al.  The aryl hydrocarbon receptor: fine-tuning the immune-response. , 2010, Current opinion in immunology.

[32]  U. Pannicke,et al.  Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt(+) innate lymphocytes. , 2010, Immunity.

[33]  J. D. Di Santo,et al.  Regulation of cytokine secretion in human CD127(+) LTi-like innate lymphoid cells by Toll-like receptor 2. , 2010, Immunity.

[34]  B. Becher,et al.  IL-12 initiates tumor rejection via lymphoid tissue–inducer cells bearing the natural cytotoxicity receptor NKp46 , 2010, Nature Immunology.

[35]  Gérard Eberl,et al.  Lineage Relationship Analysis of RORγt+ Innate Lymphoid Cells , 2010, Science.

[36]  Florence Demenais,et al.  A large-scale, consortium-based genomewide association study of asthma. , 2010, The New England journal of medicine.

[37]  R. Mebius,et al.  New insights into the development of lymphoid tissues , 2010, Nature Reviews Immunology.

[38]  J. Kaye,et al.  Shared dependence on TOX for development of lymphoid tissue inducer cell and NK cell lineages , 2010, Nature Immunology.

[39]  M. Caligiuri,et al.  Interleukin-1beta selectively expands and sustains interleukin-22+ immature human natural killer cells in secondary lymphoid tissue. , 2010, Immunity.

[40]  B. Blom,et al.  Synergy between IL-15 and Id2 Promotes the Expansion of Human NK Progenitor Cells, Which Can Be Counteracted by the E Protein HEB Required To Drive T Cell Development , 2010, The Journal of Immunology.

[41]  David J. Erle,et al.  Systemically dispersed innate IL-13–expressing cells in type 2 immunity , 2010, Proceedings of the National Academy of Sciences.

[42]  M. Colonna,et al.  Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity , 2010, Proceedings of the National Academy of Sciences.

[43]  Melody A. Swartz,et al.  Induction of Lymphoidlike Stroma and Immune Escape by Tumors That Express the Chemokine CCL21 , 2010, Science.

[44]  F. Powrie,et al.  Innate lymphoid cells drive IL-23 dependent innate intestinal pathology , 2010, Nature.

[45]  S. Nedospasov,et al.  Lymphotoxin beta receptor signaling in intestinal epithelial cells orchestrates innate immune responses against mucosal bacterial infection. , 2010, Immunity.

[46]  W. Paul,et al.  Mechanisms Underlying Lineage Commitment and Plasticity of Helper CD4+ T Cells , 2010, Science.

[47]  R. Kastelein,et al.  IL-25 elicits a multi-potent progenitor cell population that promotes Th2 cytokine responses , 2010, Nature.

[48]  A. McKenzie,et al.  Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity , 2010, Nature.

[49]  H. Spits,et al.  Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells , 2010, The Journal of experimental medicine.

[50]  J. D. Di Santo,et al.  IL-7 and IL-15 independently program the differentiation of intestinal CD3−NKp46+ cell subsets from Id2-dependent precursors , 2010, The Journal of experimental medicine.

[51]  W. Strober Immunology: The expanding TH2 universe , 2010, Nature.

[52]  Tsutomu Takeuchi,et al.  Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells , 2009, Nature.

[53]  J. Renauld,et al.  The Natural Cytotoxicity Receptor NKp46 Is Dispensable for IL-22-Mediated Innate Intestinal Immune Defense against Citrobacter rodentium1 , 2009, The Journal of Immunology.

[54]  G. Anderson,et al.  The Survival of Memory CD4+ T Cells within the Gut Lamina Propria Requires OX40 and CD30 Signals1 , 2009, The Journal of Immunology.

[55]  Andreas Lingel,et al.  Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes. , 2009, Structure.

[56]  William W. Agace,et al.  CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation , 2009, Nature Immunology.

[57]  O. Boyman,et al.  Cutting Edge: IL-7 Regulates the Peripheral Pool of Adult RORγ+ Lymphoid Tissue Inducer Cells1 , 2009, The Journal of Immunology.

[58]  H. Spits,et al.  Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from TH-17, TH1 and TH2 cells , 2009, Nature Immunology.

[59]  M. Colonna Interleukin-22-producing natural killer cells and lymphoid tissue inducer-like cells in mucosal immunity. , 2009, Immunity.

[60]  D. Littman,et al.  Plasticity of CD4+ T cell lineage differentiation. , 2009, Immunity.

[61]  M. Caligiuri,et al.  Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH 17 cytokine interleukin-22. , 2009, Blood.

[62]  H. Spits,et al.  Interleukin-22-producing innate immune cells: new players in mucosal immunity and tissue repair? , 2009, Nature Reviews Immunology.

[63]  D. Postma,et al.  Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction , 2009, Nature Genetics.

[64]  J. Lennerz,et al.  A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity , 2009, Nature.

[65]  H. Glatt,et al.  The Suggested Physiologic Aryl Hydrocarbon Receptor Activator and Cytochrome P4501 Substrate 6-Formylindolo[3,2-b]carbazole Is Present in Humans* , 2009, Journal of Biological Chemistry.

[66]  C. Tato,et al.  Lymphoid tissue inducer–like cells are an innate source of IL-17 and IL-22 , 2009, The Journal of experimental medicine.

[67]  Shinichiro Sawa,et al.  Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. , 2008, Immunity.

[68]  A. Murphy,et al.  Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. , 2008, Immunity.

[69]  Manfred Lehner,et al.  Transcription Factor E2-2 Is an Essential and Specific Regulator of Plasmacytoid Dendritic Cell Development , 2008, Cell.

[70]  E. Rickel,et al.  Identification of Functional Roles for Both IL-17RB and IL-17RA in Mediating IL-25-Induced Activities , 2008, The Journal of Immunology.

[71]  R. Kastelein,et al.  Commensal-dependent expression of IL-25 regulates the IL-23–IL-17 axis in the intestine , 2008, The Journal of experimental medicine.

[72]  B. Blom,et al.  Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix‐loop‐helix factor E2‐2 and the Ets factor Spi‐B , 2008, European journal of immunology.

[73]  Keiichiro Suzuki,et al.  Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. , 2008, Immunity.

[74]  T. Junt,et al.  Restoration of lymphoid organ integrity through the interaction of lymphoid tissue–inducer cells with stroma of the T cell zone , 2008, Nature Immunology.

[75]  J. Fujimoto,et al.  Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system. , 2008, International immunology.

[76]  T. Hibi,et al.  RORγt is dispensable for the development of intestinal mucosal T cells , 2008, Mucosal Immunology.

[77]  J. Buer,et al.  The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins , 2008, Nature.

[78]  H. Scott,et al.  Sequential phases in the development of Aire‐expressing medullary thymic epithelial cells involve distinct cellular input , 2008, European Journal of Immunology.

[79]  T. Randall,et al.  Development of secondary lymphoid organs. , 2008, Annual review of immunology.

[80]  S. Sa,et al.  Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens , 2008, Nature Medicine.

[81]  G. Anderson,et al.  Generating intrathymic microenvironments to establish T-cell tolerance , 2007, Nature Reviews Immunology.

[82]  J. Penninger,et al.  RANK signals from CD4+3− inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla , 2007, The Journal of Experimental Medicine.

[83]  É. Vivier,et al.  Natural killer cells: from CD3(-)NKp46(+) to post-genomics meta-analyses. , 2007, Current opinion in immunology.

[84]  L. Otten,et al.  Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. , 2007, Immunity.

[85]  B. Kee,et al.  Mature natural killer cell and lymphoid tissue–inducing cell development requires Id2-mediated suppression of E protein activity , 2007, The Journal of experimental medicine.

[86]  Eric Vivier,et al.  Identification, activation, and selective in vivo ablation of mouse NK cells via NKp46 , 2007, Proceedings of the National Academy of Sciences.

[87]  F. Powrie,et al.  Interleukin-23 drives innate and T cell–mediated intestinal inflammation , 2006, The Journal of experimental medicine.

[88]  D. Littman,et al.  The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells , 2006, Cell.

[89]  K. Toellner,et al.  Neonatal and Adult CD4+CD3− Cells Share Similar Gene Expression Profile, and Neonatal Cells Up-Regulate OX40 Ligand in Response to TL1A (TNFSF15)1 , 2006, The Journal of Immunology.

[90]  J. Derry,et al.  Cutting Edge: Interleukin 17 Signals through a Heteromeric Receptor Complex , 2006, The Journal of Immunology.

[91]  J. Sundberg,et al.  Abnormal Lymphoid Organ Development in Immunodeficient Mutant Mice , 2006, Veterinary pathology.

[92]  E. Kistner,et al.  Reprogramming of CTLs into natural killer–like cells in celiac disease , 2006, The Journal of experimental medicine.

[93]  M. Caligiuri,et al.  Evidence for discrete stages of human natural killer cell differentiation in vivo , 2006, The Journal of experimental medicine.

[94]  Niamh E Mangan,et al.  Identification of an interleukin (IL)-25–dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion , 2006, The Journal of experimental medicine.

[95]  T. Mcclanahan,et al.  Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract , 2006, The Journal of experimental medicine.

[96]  J Fernando Bazan,et al.  IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. , 2005, Immunity.

[97]  R. Campbell,et al.  NKp30 (NCR3) is a pseudogene in 12 inbred and wild mouse strains, but an expressed gene in Mus caroli. , 2005, Molecular biology and evolution.

[98]  P. Lane,et al.  Two sides of a cellular coin: CD4+CD3− cells regulate memory responses and lymph-node organization , 2005, Nature Reviews Immunology.

[99]  I. Mårtensson,et al.  OX40 Ligand and CD30 Ligand Are Expressed on Adult but Not Neonatal CD4+CD3− Inducer Cells: Evidence That IL-7 Signals Regulate CD30 Ligand but Not OX40 Ligand Expression1 , 2005, The Journal of Immunology.

[100]  P. Lane,et al.  Mice Deficient in OX40 and CD30 Signals Lack Memory Antibody Responses because of Deficient CD4 T Cell Memory1 , 2005, The Journal of Immunology.

[101]  D. Finke Fate and function of lymphoid tissue inducer cells. , 2005, Current opinion in immunology.

[102]  K. Asadullah,et al.  IL-22 increases the innate immunity of tissues. , 2004, Immunity.

[103]  D. Littman,et al.  Thymic Origin of Intestinal αß T Cells Revealed by Fate Mapping of RORγt+ Cells , 2004, Science.

[104]  K. Georgopoulos,et al.  Aiolos Is Required for the Generation of High Affinity Bone Marrow Plasma Cells Responsible for Long-Term Immunity , 2004, The Journal of experimental medicine.

[105]  F. Grosveld,et al.  GATA-3 Promotes Maturation, IFN-γ Production, and Liver-Specific Homing of NK Cells , 2003 .

[106]  P. Lane,et al.  CD4(+)CD3(-) accessory cells costimulate primed CD4 T cells through OX40 and CD30 at sites where T cells collaborate with B cells. , 2003, Immunity.

[107]  S. Nishikawa,et al.  Different Cytokines Induce Surface Lymphotoxin-αβ on IL-7 Receptor-α Cells that Differentially Engender Lymph Nodes and Peyer's Patches , 2002 .

[108]  R. Coffman,et al.  New IL-17 Family Members Promote Th1 or Th2 Responses in the Lung: In Vivo Function of the Novel Cytokine IL-251 , 2002, The Journal of Immunology.

[109]  T. Iwanaga,et al.  Identification of Multiple Isolated Lymphoid Follicles on the Antimesenteric Wall of the Mouse Small Intestine1 , 2002, The Journal of Immunology.

[110]  M. Leach,et al.  IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. , 2001, Immunity.

[111]  Angel Porgador,et al.  Recognition of viral hemagglutinins by NKp44 but not by NKp30 , 2001, European journal of immunology.

[112]  Irving L. Weissman,et al.  The Fetal Liver Counterpart of Adult Common Lymphoid Progenitors Gives Rise to All Lymphoid Lineages, CD45+CD4+CD3− Cells, As Well As Macrophages1 , 2001, The Journal of Immunology.

[113]  R. Flavell,et al.  Cutting Edge: Critical Role of Inducible Costimulator in Germinal Center Reactions1 , 2001, The Journal of Immunology.

[114]  Angel Porgador,et al.  Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells , 2001, Nature.

[115]  A. Bakker,et al.  Id2 and Id3 Inhibit Development of Cd34+ Stem Cells into Predendritic Cell (Pre-Dc)2 but Not into Pre-Dc1 , 2000, The Journal of experimental medicine.

[116]  Steffen Jung,et al.  Regulation of Peripheral Lymph Node Genesis by the Tumor Necrosis Factor Family Member Trance , 2000, The Journal of experimental medicine.

[117]  R. Barndt,et al.  Functions of E2A-HEB Heterodimers in T-Cell Development Revealed by a Dominant Negative Mutation of HEB , 2000, Molecular and Cellular Biology.

[118]  F. Zhang,et al.  Retinoid-related orphan receptor γ (RORγ) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis , 2000 .

[119]  A. Pierani,et al.  Requirement for RORgamma in thymocyte survival and lymphoid organ development. , 2000, Science.

[120]  M. Bevan,et al.  Down-Regulation of the Orphan Nuclear Receptor RORγt Is Essential for T Lymphocyte Maturation1 , 2000, The Journal of Immunology.

[121]  I. Villey,et al.  RORγT, a thymus‐specific isoform of the orphan nuclear receptor RORγ / TOR, is up‐regulated by signaling through the pre‐T cell receptor and binds to the TEA promoter , 1999, European journal of immunology.

[122]  M. Heemskerk,et al.  Genetic modification of human B-cell development: B-cell development is inhibited by the dominant negative helix loop helix factor Id3. , 1999, Blood.

[123]  C. Meisel,et al.  Crucial Role of the Interleukin 1 Receptor Family Member T1/St2 in T Helper Cell Type 2–Mediated Lung Mucosal Immune Responses , 1999, The Journal of experimental medicine.

[124]  W. Dougall,et al.  RANK is essential for osteoclast and lymph node development. , 1999, Genes & development.

[125]  S. Nishikawa,et al.  IL-7 receptor alpha+ CD3(-) cells in the embryonic intestine induces the organizing center of Peyer's patches. , 1999, International immunology.

[126]  Ahmed Mansouri,et al.  Development of peripheral lymphoid organs and natural killer cells depends on the helix–loop–helix inhibitor Id2 , 1999, Nature.

[127]  S. Morony,et al.  OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis , 1999, Nature.

[128]  E. Ingulli,et al.  Visualization of specific B and T lymphocyte interactions in the lymph node. , 1998, Science.

[129]  F. Mackay,et al.  Lymph Node Genesis Is Induced by Signaling through the Lymphotoxin β Receptor , 1998 .

[130]  G. Nolan,et al.  Inhibition of T Cell and Promotion of Natural Killer Cell Development by the Dominant Negative Helix Loop Helix Factor Id3 , 1997, The Journal of experimental medicine.

[131]  I. Weissman,et al.  Developing lymph nodes collect CD4+CD3- LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. , 1997, Immunity.

[132]  D. Pinkel,et al.  E2A deficiency leads to abnormalities in alphabeta T-cell development and to rapid development of T-cell lymphomas , 1997, Molecular and cellular biology.

[133]  A. Feeney,et al.  Both E12 and E47 allow commitment to the B cell lineage. , 1997, Immunity.

[134]  F. Mackay,et al.  Surface lymphotoxin alpha/beta complex is required for the development of peripheral lymphoid organs , 1996, The Journal of experimental medicine.

[135]  K. Ikuta,et al.  Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+ IL-7R+ Thy1+ lympho-hemopoietic progenitors develop , 1996, The Journal of experimental medicine.

[136]  H. Nakauchi,et al.  Developmental defects of lymphoid cells in Jak3 kinase-deficient mice. , 1995, Immunity.

[137]  C. Ware,et al.  Mouse lymphotoxin-beta receptor. Molecular genetics, ligand binding, and expression. , 1995, Journal of immunology.

[138]  W. Leonard,et al.  Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. , 1995, Immunity.

[139]  M. Zafari,et al.  Characterization of surface lymphotoxin forms. Use of specific monoclonal antibodies and soluble receptors. , 1995, Journal of immunology.

[140]  A. Jetten,et al.  ROR gamma: the third member of ROR/RZR orphan receptor subfamily that is highly expressed in skeletal muscle. , 1994, Biochemical and biophysical research communications.

[141]  K. Kelly,et al.  Seeding of neonatal lymph nodes by T cells and identification of a novel population of CD3−CD4+ cells , 1992, European journal of immunology.

[142]  Jun Zhang,et al.  Sites of specific B cell activation in primary and secondary responses to T cell‐dependent and T cell‐independent antigens , 1991, European journal of immunology.

[143]  L. Lanier,et al.  Transcriptional control of natural killer cell development and function. , 2011, Advances in immunology.

[144]  H. Spits,et al.  The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling , 2011, Nature Immunology.

[145]  Tsutomu Takeuchi,et al.  Natural helper cells: a new player in the innate immune response against helminth infection. , 2010, Advances in immunology.

[146]  Andreas Diefenbach,et al.  RORγt and commensal microflora are required for the differentiation of mucosal interleukin 22–producing NKp46+ cells , 2009, Nature Immunology.

[147]  H. Spits,et al.  Human fetal lymphoid tissue–inducer cells are interleukin 17–producing precursors to RORC+ CD127+ natural killer–like cells , 2009, Nature Immunology.

[148]  J. Banchereau,et al.  Influence of the transcription factor RORγt on the development of NKp46+ cell populations in gut and skin , 2009, Nature Immunology.

[149]  L. Coussens,et al.  Paradoxical roles of the immune system during cancer development , 2006, Nature Reviews Cancer.

[150]  Yongwon Choi,et al.  An essential function for the nuclear receptor RORγt in the generation of fetal lymphoid tissue inducer cells , 2004, Nature Immunology.

[151]  W. Vermi,et al.  Lymph node pathology in primary combined immunodeficiency diseases , 2004, Springer Seminars in Immunopathology.

[152]  C. Murre,et al.  E protein function in lymphocyte development. , 2002, Annual review of immunology.

[153]  W. Paul,et al.  The IL-4 receptor: signaling mechanisms and biologic functions. , 1999, Annual review of immunology.

[154]  S. Nishikawa,et al.  Essential role of IL-7 receptor alpha in the formation of Peyer's patch anlage. , 1998, International immunology.