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Functional Defects in Type 3 Innate Lymphoid Cells and Classical Monocytes in a Patient with Hyper-IgE Syndrome

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Hyper-IgE syndrome (HIES) is a very rare primary immune deficiency characterized by elevated serum IgE levels, recurrent bacterial infections, chronic dermatitis, and connective tissue abnormalities. Autosomal dominant (AD) HIES involves a mutation in signal transducer and activator of transcription 3 (STAT3) that leads to an impaired TH17 response. STAT3 signaling is also involved in the function of RORγt+ type 3 innate lymphoid cells (ILC3s) and RORγt+TH17 cells. The aim of this study was to investigate the role of innate immune cells such as innate lymphoid cells (ILCs), granulocytes, and monocytes in a patient with HIES. Peripheral blood mononuclear cells (PBMCs) from a patient with HIES and three age-matched healthy controls were obtained for the analysis of the innate and adaptive immune cells. The frequencies of ILCs in PBMCs were lower in the patient with HIES than in the controls. Moreover, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A produced by ILC3s in PBMCs were lower in the patient with HIES than the controls. Compared with the controls, classical monocytes (CD14+CD16low), which have a high antimicrobial capability, were also lower in the patient with HIES, while non-classical monocytes (CD14lowCD16+) as well as intermediate monocytes (CD14+CD16intermediate) were higher. Taken together, these results indicate that the impaired immune defense against pathogenic microbes in the patient with HIES might be partially explained by functional defects in ILC3s and inflammatory monocytes.

Abstract

Hyper-IgE syndrome (HIES) is a very rare primary immune deficiency characterized by elevated serum IgE levels, recurrent bacterial infections, chronic dermatitis, and connective tissue abnormalities. Autosomal dominant (AD) HIES involves a mutation in signal transducer and activator of transcription 3 (STAT3) that leads to an impaired TH17 response. STAT3 signaling is also involved in the function of RORγt+ type 3 innate lymphoid cells (ILC3s) and RORγt+TH17 cells. The aim of this study was to investigate the role of innate immune cells such as innate lymphoid cells (ILCs), granulocytes, and monocytes in a patient with HIES. Peripheral blood mononuclear cells (PBMCs) from a patient with HIES and three age-matched healthy controls were obtained for the analysis of the innate and adaptive immune cells. The frequencies of ILCs in PBMCs were lower in the patient with HIES than in the controls. Moreover, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A produced by ILC3s in PBMCs were lower in the patient with HIES than the controls. Compared with the controls, classical monocytes (CD14+CD16low), which have a high antimicrobial capability, were also lower in the patient with HIES, while non-classical monocytes (CD14lowCD16+) as well as intermediate monocytes (CD14+CD16intermediate) were higher. Taken together, these results indicate that the impaired immune defense against pathogenic microbes in the patient with HIES might be partially explained by functional defects in ILC3s and inflammatory monocytes.

참고문헌 (37)

  1. Heimall J, "Pathogenesis of hyper IgE syndrome", Clin Rev Allergy Immunol, 38, pp.32~38 (2010)
  2. Holland SM, "STAT3 mutations in the hyper-IgE syndrome", N Engl J Med, 357, pp.1608~1619 (2007)
  3. Minegishi Y, "Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity", Immunity, 25, pp.745~755 (2006)
  4. Zhang Q, "Combined immunodeficiency associated with DOCK8 mutations", N Engl J Med, 361, pp.2046~2055 (2009)
  5. Saito M, "Defective IL-10 signaling in hyper-IgE syndrome results in impaired generation of tolerogenic dendritic cells and induced regulatory T cells", J Exp Med, 208, pp.235~249 (2011)
  6. Lin JX, "The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15", Immunity, 2, pp.331~339 (1995)
  7. Wei L, "IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner", J Biol Chem, 282, pp.34605~34610 (2007)
  8. Hankey PA., "Regulation of hematopoietic cell development and function by Stat3", Front Biosci (Landmark Ed), 14, pp.5273~5290 (2009)
  9. de Jong PR, "STAT3 regulates monocyte TNF-alpha production in systemic inflammation caused by cardiac surgery with cardiopulmonary bypass", PLoS One, 7, pp.e35070~ (2012)
  10. Milner JD, "Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome", Nature, 452, pp.773~776 (2008)
  11. Ma CS, "Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3", J Exp Med, 205, pp.1551~1557 (2008)
  12. Laan M, "Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways", J Immunol, 162, pp.2347~2352 (1999)
  13. Minegishi Y, "Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome", J Exp Med, 206, pp.1291~1301 (2009)
  14. Hill HR, "Defect in neutrophil granulocyte chemotaxis in Job's syndrome of recurrent “cold” staphylococcal abscesses", Lancet, 2, pp.617~619 (1974)
  15. Buckley RH, "Abnormalities in the regulation of human IgE synthesis", Immunol Rev, 41, pp.288~314 (1978)
  16. Giacomelli M, "SH2-domain mutations in STAT3 in hyper-IgE syndrome patients result in impairment of IL-10 function", Eur J Immunol, 41, pp.3075~3084 (2011)
  17. Yeganeh M, "Toll-like receptor stimulation induces higher TNF-alpha secretion in peripheral blood mononuclear cells from patients with hyper IgE syndrome", Int Arch Allergy Immunol, 146, pp.190~194 (2008)
  18. Panopoulos AD, "STAT3 governs distinct pathways in emergency granulopoiesis and mature neutrophils", Blood, 108, pp.3682~3690 (2006)
  19. Moniuszko M, "Enhanced frequencies of CD14++CD16+, but not CD14+CD16+, peripheral blood monocytes in severe asthmatic patients", Clin Immunol, 130, pp.338~346 (2009)
  20. Wong KL, "The three human monocyte subsets: implications for health and disease", Immunol Res, 53, pp.41~57 (2012)
  21. Artis D, "The biology of innate lymphoid cells", Nature, 517, pp.293~301 (2015)
  22. Chang YJ, "Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity", Nat Immunol, 12, pp.631~638 (2011)
  23. Kim HY, "Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity", Nat Med, 20, pp.54~61 (2014)
  24. Wang WB, "STAT3 negatively regulates type I IFN-mediated antiviral response", J Immunol, 187, pp.2578~2585 (2011)
  25. Gutierrez-Hincapié S, "Quantitative defects in invariant NKT cells and TLR responses in patients with hyper-IgE syndrome", Allergol Immunopathol (Madr), 43, pp.553~561 (2015)
  26. Xiong H, "Innate Lymphocyte", Ly6C(hi) monocyte crosstalk promotes klebsiella pneumoniae clearance, 2016, pp.165, 679~689
  27. Minegishi Y, "Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome", Nature, 448, pp.1058~1062 (2007)
  28. Taga T, "Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130", Cell, 58, pp.573~581 (1989)
  29. O'Shea JJ, "JAK and STAT signaling molecules in immunoregulation and immune-mediated disease", Immunity, 36, pp.542~550 (2012)
  30. Del Prete G, "Defective in vitro production of gamma-interferon and tumor necrosis factor-alpha by circulating T cells from patients with the hyper-immunoglobulin E syndrome", J Clin Invest, 84, pp.1830~1835 (1989)
  31. Guo X, "Induction of innate lymphoid cell-derived interleukin-22 by the transcription factor STAT3 mediates protection against intestinal infection", Immunity, 40, pp.25~39 (2014)
  32. Ziegler-Heitbrock L, "Toward a refined definition of monocyte subsets", Front Immunol, 4, pp.23~ (2013)
  33. Cooper DL, "FcγRIIIa expression on monocytes in rheumatoid arthritis: role in immune-complex stimulated TNF production and non-response to methotrexate therapy", PLoS One, 7, pp.e28918~ (2012)
  34. Schauer D, "Intermediate monocytes but not TIE2-expressing monocytes are a sensitive diagnostic indicator for colorectal cancer", PLoS One, 7, pp.e44450~ (2012)
  35. Skrzeczyńska-Moncznik J, "Peripheral blood CD14high CD16+ monocytes are main producers of IL-10", Scand J Immunol, 67, pp.152~159 (2008)
  36. Tsukamoto M, "CD14(bright)CD16+ intermediate monocytes are induced by interleukin-10 and positively correlate with disease activity in rheumatoid arthritis", Arthritis Res Ther, 19, pp.28~ (2017)
  37. Grimbacher B, "Hyper-IgE syndromes", Immunol Rev, 203, pp.244~250 (2005)

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