Do studies in humans better depict Th17 cells?

CD4(+) T helper (Th) lymphocytes represent a heterogeneous population of cells. In addition to type 1 (Th1) and type 2 (Th2) cells, another subset of CD4(+) effector Th cells has been discovered and named as Th17, because of its unique ability to produce interleukin (IL)-17. Studies in mice initially suggested that Th17 cells are the pathogenic cells in autoimmune disorders, whereas Th1 cells may behave rather as protective. Subsequent studies in humans demonstrated the plasticity of Th17 cells and their possibility to shift to Th1. The plasticity of Th17 to Th1 cells has recently been confirmed in mice, where it was found that Th17 cells seem to be pathogenic only when they shift to Th1 cells. Studies in humans also showed that Th17 cells are different than in mice because all of them express CD161 and exclusively originate from CD161(+) precursors present in umbilical cord blood and newborn thymus. While murine Th17 cells develop in response to IL-6, IL-1, and transforming growth factor (TGF)-beta, human Th17 cells originate from these CD161(+) precursors in response to IL-1beta and IL-23, the need for TGF-beta being controversial. Thus, we believe that studies in humans have better depicted human Th17 cells than studies in mice.

[1]  Ho‐Youn Kim,et al.  Expression of IL-17 homologs and their receptors in the synovial cells of rheumatoid arthritis patients. , 2005, Molecules and cells.

[2]  J. O’Shea,et al.  Th17 cells: a new fate for differentiating helper T cells , 2008, Immunologic research.

[3]  R. Nurieva,et al.  Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. , 2009, Immunity.

[4]  J. Kolls,et al.  Th17 cytokines and mucosal immunity , 2008, Immunological reviews.

[5]  Kathleen M. Smith,et al.  Development, cytokine profile and function of human interleukin 17–producing helper T cells , 2007, Nature Immunology.

[6]  C. Elson,et al.  Late developmental plasticity in the T helper 17 lineage. , 2009, Immunity.

[7]  T. Mcclanahan,et al.  Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation , 2003, The Journal of experimental medicine.

[8]  S. Goya,et al.  Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17 , 2008, The Journal of experimental medicine.

[9]  L Adorini,et al.  The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. , 1998, Annual review of immunology.

[10]  S. Tangye,et al.  Functional Consequences of Interactions between Human NKR-P1A and Its Ligand LLT1 Expressed on Activated Dendritic Cells and B Cells1 , 2008, The Journal of Immunology.

[11]  M. Veldhoen,et al.  Differentiation of human TH-17 cells does require TGF-β! , 2008, Nature Immunology.

[12]  C. Gordon,et al.  Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin , 2005, Arthritis research & therapy.

[13]  W. Cowden,et al.  IFN-gamma is critical to the control of murine autoimmune encephalomyelitis and regulates both in the periphery and in the target tissue: a possible role for nitric oxide. , 1999, Journal of immunology.

[14]  R. Coffman,et al.  Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. , 1986, Journal of immunology.

[15]  L. Steinman.  A rush to judgment on Th17 , 2008, The Journal of experimental medicine.

[16]  S. Romagnani,et al.  The Th1/Th2 paradigm. , 1997, Immunology today.

[17]  L. Lanier,et al.  Human NKR-P1A. A disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes. , 1994, Journal of immunology.

[18]  C. Tato,et al.  Distinct regulation of interleukin-17 in human T helper lymphocytes. , 2007, Arthritis and rheumatism.

[19]  L. Cosmi,et al.  Phenotypic and functional features of human Th17 cells , 2007, The Journal of experimental medicine.

[20]  I. McInnes,et al.  IL‐35 is a novel cytokine with therapeutic effects against collagen‐induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells , 2007, European journal of immunology.

[21]  L. Cosmi,et al.  Human interleukin 17–producing cells originate from a CD161+CD4+ T cell precursor , 2008, The Journal of experimental medicine.

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

[23]  F. Sallusto,et al.  Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. , 2007, Nature immunology.

[24]  Y. Iwakura,et al.  Development of Proteoglycan-Induced Arthritis Is Independent of IL-171 , 2008, The Journal of Immunology.

[25]  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.

[26]  J Wagner,et al.  Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. , 2000, Immunity.

[27]  D. Jarrossay,et al.  Surface phenotype and antigenic specificity of human interleukin 17–producing T helper memory cells , 2007, Nature Immunology.

[28]  R. D. Hatton,et al.  Transforming growth factor-beta induces development of the T(H)17 lineage. , 2006, Nature.

[29]  L. Cosmi,et al.  TGF‐β indirectly favors the development of human Th17 cells by inhibiting Th1 cells , 2009, European journal of immunology.

[30]  R. Kastelein,et al.  Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain , 2003, Nature.

[31]  D. Bending,et al.  Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice. , 2009, The Journal of clinical investigation.

[32]  R. J. Hocking,et al.  TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. , 2006, Immunity.

[33]  D. Littman,et al.  The differentiation of human TH-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt , 2008, Nature Immunology.

[34]  H. Weiner,et al.  Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells , 2006, Nature.

[35]  Chen Dong,et al.  T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. , 2008, Immunity.

[36]  E. Huarte,et al.  PILAR is a novel modulator of human T-cell expansion. , 2008, Blood.

[37]  Sergio Romagnani,et al.  Human Th17 cells: Are they different from murine Th17 cells? , 2009, European journal of immunology.

[38]  M. Veldhoen,et al.  Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells , 2009, The Journal of experimental medicine.

[39]  D. Hommes,et al.  Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. , 2007, Immunity.

[40]  P. Kivisäkk,et al.  Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis , 1999, Multiple sclerosis.

[41]  T. Mcclanahan,et al.  The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17–producing effector T helper cells in vivo , 2009, Nature Immunology.

[42]  Jay K Kolls,et al.  The Biological Functions of T Helper 17 Cell Effector Cytokines in Inflammation , 2022 .

[43]  C. Albanesi,et al.  IL-17 Is Produced by Nickel-Specific T Lymphocytes and Regulates ICAM-1 Expression and Chemokine Production in Human Keratinocytes: Synergistic or Antagonist Effects with IFN-γ and TNF-α , 1999, The Journal of Immunology.

[44]  Albert Bendelac,et al.  The biology of NKT cells. , 2007, Annual review of immunology.

[45]  B. Becher,et al.  IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. , 2008, The Journal of clinical investigation.

[46]  Mark M Davis,et al.  A prescription for human immunology. , 2008, Immunity.

[47]  Y. Iwakura,et al.  Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category , 2008, The Journal of experimental medicine.

[48]  W. Cowden,et al.  IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. , 1996, Journal of immunology.

[49]  L. Fouser,et al.  Th17 cytokines and their emerging roles in inflammation and autoimmunity , 2008, Immunological reviews.

[50]  K. Boyd,et al.  The inhibitory cytokine IL-35 contributes to regulatory T-cell function , 2007, Nature.

[51]  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.

[52]  D. Vignali,et al.  Interleukin‐35: odd one out or part of the family? , 2008, Immunological reviews.

[53]  M. Kapsenberg,et al.  Interleukin-17 in inflammatory skin disorders , 2007, Current opinion in allergy and clinical immunology.

[54]  P. Valdez,et al.  Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis , 2007, Nature.

[55]  M. Huber,et al.  IRF4 is essential for IL-21-mediated induction, amplification, and stabilization of the Th17 phenotype , 2008, Proceedings of the National Academy of Sciences.

[56]  T. Owens,et al.  Interferon‐γ confers resistance to experimental allergic encephalomyelitis , 1996, European journal of immunology.

[57]  A. Rachitskaya,et al.  Cutting Edge: NKT Cells Constitutively Express IL-23 Receptor and RORγt and Rapidly Produce IL-17 upon Receptor Ligation in an IL-6-Independent Fashion1 , 2008, The Journal of Immunology.

[58]  T. Mcclanahan,et al.  #2202: Mucosal Autoimmunity Saturday, June 13 10:45 am–11:00 amCirculating and Gut-resident Human Th17 Cells Express CD161 and Promote Intestinal Inflammation , 2009 .

[59]  L. Lanier,et al.  Cutting Edge: Lectin-Like Transcript-1 Is a Ligand for the Inhibitory Human NKR-P1A Receptor1 , 2005, The Journal of Immunology.

[60]  L. Cosmi,et al.  Phenotypic and functional features of human Th 17 cells , 2007 .

[61]  E. Barillot,et al.  A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses , 2008, Nature Immunology.

[62]  A. Lovett-racke,et al.  T-bet Regulates the Fate of Th1 and Th17 Lymphocytes in Autoimmunity1 , 2007, The Journal of Immunology.

[63]  Lars Rogge,et al.  Faculty Opinions recommendation of IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. , 2008 .

[64]  J. O’Shea,et al.  Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation. , 2007, Seminars in immunology.

[65]  Hiromu Ito,et al.  Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model , 2007, The Journal of experimental medicine.

[66]  A. Sher,et al.  IL-23 plays a key role in Helicobacter hepaticus–induced T cell–dependent colitis , 2006, The Journal of experimental medicine.

[67]  B. Segal,et al.  IL-12– and IL-23–modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition , 2008, The Journal of experimental medicine.

[68]  O. Arican,et al.  Serum Levels of TNF-α, IFN-γ, IL-6, IL-8, IL-12, IL-17, and IL-18 in Patients With Active Psoriasis and Correlation With Disease Severity , 2005, Mediators of inflammation.

[69]  J. Edmonds,et al.  Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort). , 2006, Arthritis and rheumatism.

[70]  Yuka Kanno,et al.  Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. , 2009, Immunity.

[71]  Yi-hong Wang,et al.  Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells , 2009, European journal of immunology.

[72]  S. Romagnani.  Human TH1 and TH2 subsets: doubt no more. , 1991, Immunology today.