Upregulation of Interleukin 21 and Promotion of Interleukin 17 Production in Chronic or Recurrent Vogt-Koyanagi-Harada Disease | Infectious Diseases | JAMA Ophthalmology | JAMA Network
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Read  RWRao  NACunningham  ET Vogt-Koyanagi-Harada disease.  Curr Opin Ophthalmol 2000;11 (6) 437- 442PubMedGoogle ScholarCrossref
Li  BYang  PZhou  H  et al.  Upregulation of T-bet expression in peripheral blood mononuclear cells during Vogt-Koyanagi-Harada disease.  Br J Ophthalmol 2005;89 (11) 1410- 1412PubMedGoogle ScholarCrossref
Sugita  STakase  HTaguchi  C  et al.  Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens.  Invest Ophthalmol Vis Sci 2006;47 (6) 2547- 2554PubMedGoogle ScholarCrossref
Chi  WYang  PLi  B  et al.  IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease.  J Allergy Clin Immunol 2007;119 (5) 1218- 1224PubMedGoogle ScholarCrossref
Fina  DSarra  MFantini  MC  et al.  Regulation of gut inflammation and Th17 cell response by interleukin-21.  Gastroenterology 2008;134 (4) 1038- 1048PubMedGoogle ScholarCrossref
Liu  ZYang  LCui  Y  et al.  Il-21 enhances NK cell activation and cytolytic activity and induces Th17 cell differentiation in inflammatory bowel disease.  Inflamm Bowel Dis 2009;15 (8) 1133- 1144PubMedGoogle ScholarCrossref
Korn  TBettelli  EGao  W  et al.  IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells.  Nature 2007;448 (7152) 484- 487PubMedGoogle ScholarCrossref
Nurieva  RYang  XOMartinez  G  et al.  Essential autocrine regulation by IL-21 in the generation of inflammatory T cells.  Nature 2007;448 (7152) 480- 483PubMedGoogle ScholarCrossref
Spolski  RKashyap  MRobinson  CYu  ZLeonard  WJ IL-21 signaling is critical for the development of type I diabetes in the NOD mouse.  Proc Natl Acad Sci U S A 2008;105 (37) 14028- 14033PubMedGoogle ScholarCrossref
Spolski  RLeonard  WJ Interleukin-21: basic biology and implications for cancer and autoimmunity.  Annu Rev Immunol 2008;2657- 79PubMedGoogle ScholarCrossref
Monteleone  GMonteleone  IFina  D  et al.  Interleukin-21 enhances T-helper cell type I signaling and interferon-γ production in Crohn's disease.  Gastroenterology 2005;128 (3) 687- 694PubMedGoogle ScholarCrossref
Young  DAHegen  MMa  HL  et al.  Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis.  Arthritis Rheum 2007;56 (4) 1152- 1163PubMedGoogle ScholarCrossref
Li  JShen  WKong  KLiu  Z Interleukin-21 induces T-cell activation and proinflammatory cytokine secretion in rheumatoid arthritis.  Scand J Immunol 2006;64 (5) 515- 522PubMedGoogle ScholarCrossref
Caruso  RBotti  ESarra  M  et al.  Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis.  Nat Med 2009;15 (9) 1013- 1015PubMedGoogle ScholarCrossref
Jones  JLPhuah  CLCox  AL  et al.  IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H).  J Clin Invest 2009;119 (7) 2052- 2061PubMedGoogle Scholar
Distler  JHJüngel  AKowal-Bielecka  O  et al.  Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis.  Arthritis Rheum 2005;52 (3) 856- 864PubMedGoogle ScholarCrossref
Wang  XFYuan  SLJiang  L  et al.  Changes of serum BAFF and IL-21 levels in patients with systemic lupus erythematosus and their clinical significance [in Chinese].  Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2007;23 (11) 1041- 1042PubMedGoogle Scholar
Herber  DBrown  TPLiang  SYoung  DACollins  MDunussi-Joannopoulos  K  IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression.  J Immunol 2007;178 (6) 3822- 3830PubMedGoogle ScholarCrossref
Read  RWHolland  GNRao  NA  et al.  Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature.  Am J Ophthalmol 2001;131 (5) 647- 652PubMedGoogle ScholarCrossref
Ozaki  KSpolski  REttinger  R  et al.  Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6.  J Immunol 2004;173 (9) 5361- 5371PubMedGoogle ScholarCrossref
Yuan  SLJiang  LZhang  XLLi  SFDuan  HMWang  XF Serum IL-21 level in patients with primary Sjogren's syndrome and clinical significance of IL-21 [in Chinese.  Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2007;23 (2) 124- 126PubMedGoogle Scholar
Caprioli  FSarra  MCaruso  R  et al.  Autocrine regulation of IL-21 production in human T lymphocytes.  J Immunol 2008;180 (3) 1800- 1807PubMedGoogle ScholarCrossref
Chatterjee  RBatra  JGhosh  B A common exonic variant of interleukin21 confers susceptibility to atopic asthma.  Int Arch Allergy Immunol 2009;148 (2) 137- 146PubMedGoogle ScholarCrossref
Bubier  JASproule  TJForeman  O  et al.  A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice.  Proc Natl Acad Sci U S A 2009;106 (5) 1518- 1523PubMedGoogle ScholarCrossref
Sonderegger  IKisielow  JMeier  RKing  CKopf  M IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo.  Eur J Immunol 2008;38 (7) 1833- 1838PubMedGoogle ScholarCrossref
Wurster  ALRodgers  VLSatoskar  AR  et al.  Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon γ-producing Th1 cells.  J Exp Med 2002;196 (7) 969- 977PubMedGoogle ScholarCrossref
King  CTangye  SGMackay  CR T follicular helper (TFH) cells in normal and dysregulated immune responses.  Annu Rev Immunol 2008;26741- 766PubMedGoogle ScholarCrossref
Laboratory Sciences
November 8, 2010

Upregulation of Interleukin 21 and Promotion of Interleukin 17 Production in Chronic or Recurrent Vogt-Koyanagi-Harada Disease

Author Affiliations

Author Affiliations: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (Ms Li), The First Affiliated Hospital of Chongqing Medical University, Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing (Mss Li and Wang and Drs Yang, Liu, and Hou), and Department of Ophthalmology, The Second Hospital of Jilin University, Changchun (Dr Liu), China; and Eye Research Institute Maastricht and Department of Ophthalmology, University Hospital Maastricht, Maastricht, the Netherlands (Dr Kijlstra).

Arch Ophthalmol. 2010;128(11):1449-1454. doi:10.1001/archophthalmol.2010.265

Objectives  To analyze the expression and potential role of interleukin (IL) 21 in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.

Methods  Blood samples were obtained from patients with VKH disease and from healthy control subjects. Serum IL-21 level and IL-21 messenger RNA (mRNA) expression by peripheral blood mononuclear cells (PBMCs) were determined by enzyme-linked immunosorbent assay and by reverse transcriptase–polymerase chain reaction, respectively. Interleukin 17 and interferon γ levels in the supernatants of PBMCs and CD4+ T cells cultured with anti-CD3 and anti-CD28 antibodies in the presence or absence of recombinant IL-21 were detected by enzyme-linked immunosorbent assay.

Results  The results showed a significantly increased serum IL-21 level, as well as higher IL-21 mRNA expression by PBMCs, in patients having chronic or recurrent active VKH disease compared with patients having inactive VKH disease and with controls. In vitro experiments showed that recombinant IL-21 significantly increased IL-17 production by PBMCs and by CD4+ T cells from patients and from controls. However, recombinant IL-21 did not affect interferon γ expression by PBMCs or by CD4+ T cells.

Conclusion  Interleukin 21 may be involved in the pathogenesis of chronic or recurrent VKH disease, possibly by promoting IL-17 secretion.

Clinical Relevance  Findings from the present study suggest that IL-21 may be a potential target in the development of therapy for VKH disease.