Horm Metab Res 2008; 40(11): 767-771
DOI: 10.1055/s-2008-1080896
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Reduced Frequency of Peripheral Plasmacytoid Dendritic Cells in Type 1 Diabetes

C. Hinkmann 1 , I. Knerr 2 , E-G. Hahn 1 , T. Lohmann 1 [] , C. C. Seifarth 1
  • 1Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
  • 2Department of Pediatrics, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
Further Information

Publication History

received 30.01.2008

accepted 10.03.2008

Publication Date:
11 July 2008 (online)

Abstract

Dendritic cells (DCs) as antigen presenting cells play an important role in the initiation of an autoimmune disease like type 1 diabetes. Although there is evidence from the NOD mouse model that the function and frequency of DCs is altered in type 1 diabetes, there is little data on dendritic cells in human type 1 diabetes. We investigated peripheral blood myeloid (mDC1 and mDC2) and plasmacytoid dendritic cells (pDCs) in 15 type 1 diabetes patients with recent onset (within the last 3 months) of type 1 diabetes as well as in 15 patients with long standing (more than 5 years) type 1 diabetes by flow cytometry. Both groups were compared to age matched controls. We observed a significantly reduced percentage of pDCs of peripheral blood mononuclear cells (PBMCs) in both recent onset (0.13 vs. 0.25%, p=0.01) and long standing type 1 diabetes patients (0.13 vs. 0.24%, p=0.01). The absolute counts of pDCs per ml of blood were also significantly lower in both recent onset (mean 9560 vs. 13524, p=0.048) and long-standing diabetes (mean 7869 vs. 12202; p=0.05). The percentage of mDC1 was significantly diminished in recent onset (0.21% vs. 0.30%, p=0.034), but not in long standing type 1 diabetes. Our study demonstrates a persisting reduction of peripheral plasmacytoid DCs in type 1 diabetes patients. Since pDCs are involved in the control of immune responses and inducing regulatory cells, a reduced number of pDCs may predispose to an autoimmune reaction in the pancreatic islets.

References

  • 1 Aoki CA, Borchers AT, Ridgway WM, Keen CL, Ansari AA, Gershwin ME. NOD mice and autoimmunity.  Autoimmun Rev. 2005;  4 373-379
  • 2 Tisch R, MacDevitt H. Insulin-dependent diabetes mellitus.  Cell. 1996;  85 291-297
  • 3 Banchereau J, Steinman RM. Dendritic cells and the control of immunity.  Nature. 1998;  392 245-252
  • 4 Steinman RM. The dendritic cell system and its role in immunogenicity.  Annu Rev Immunol. 1991;  9 271-296
  • 5 Shinomiya M, Nadano S, Shinomiya H, Onji M. In situ characterization of dendritic cells occurring in the islets of nonobese diabetic mice during the development of insulitis.  Pancreas. 2000;  20 290-296
  • 6 Rosmalen JG, Leenen PJ, Katz JD, Voerman JS, Drexhage HA. Dendritic cells in the autoimmune insulitis in NOD mouse models of diabetes.  Adv Exp Med Biol. 1997;  417 291-294
  • 7 Dzionek A, Fuchs A, Schmidt P, Cremer S, Zysk M, Miltenyi S, Buck DW, Schmitz J. BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood.  J Immunol. 2001;  65 6037-6046
  • 8 Robinson SP, Patterson S, English N, Davies D, Knight SC, Reid CD. Human peripheral blood contains two distinct lineages of dendritic cells.  Eur J Immun. 1999;  29 2769-2778
  • 9 Rissoan MC, Soumelis V, Kadowaki N, Grouard G, Briere F, Waal Malefyt R de, Liu YJ. Reciprocal control of T helper cell and dendritic cell differentiation.  Science. 1999;  283 1183-1186
  • 10 Penna G, Sozzani S, Adorini L. Cutting edge: selective usage of chemokine receptors by plasmacytoid dendritic cells.  J Immunol. 2001;  167 1862-1866
  • 11 Jacobs B, Wuttke M, Papewalis C, Seissler J, Schott M. Dendritic cell subtypes and in vitro generation of dendritic cells.  Horm Metab Res. 2008;  40 99-107
  • 12 Jonuleit H, Schmitt E, Steinbrink K, Enk AH. Dendritic cells as a tool to induce anergic and regulatory T cells.  Trends Immunol. 2001;  22 394-400
  • 13 Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H, Lanzavecchia A, Colonna M. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon.  Nat Med. 1999;  5 919-923
  • 14 Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K, Ho S, Antonenko S, Liu YJ. The nature of the principal type 1 interferon-producing cells in human blood.  Science. 1999;  284 ((5421)) 1835-1837
  • 15 Chang CC, Wright A, Punnonen J. Monocyte-derived CD1a+and CD1a- dendritic cell subsets differ in their cytokine production profiles, susceptibilities to transfection, and capacities to direct Th cell differentiation.  J Immunol. 2000;  165 3584-3591
  • 16 Ito T, Amakawa R, Inaba M, Ikehara S, Inaba K, Fukuhara S. Differential regulation of human blood dendritic cell subsets by IFNs.  J Immunol. 2001;  166 2961-2969
  • 17 Green EA, Eynon EE, Flavell RA. Local expression of TNFalpha in neonatal NOD mice promotes diabetes by enhancing presentation of islet antigens.  Immunity. 1998;  9 733-743
  • 18 Boudaly S, Morin J, Berthier R, Marche P, Boitard C. Altered dendritic cells (DC) might be responsible for regulatory T cell imbalance and autoimmunity in nonobese diabetic (NOD) mice.  Eur Cytokine Netw. 2002;  13 29-37
  • 19 Weaver Jr DJ, Poligone B, Bui T, Abdel-Motal UM, Baldwin Jr AS, Tisch R. Dendritic cells from nonobese diabetic mice exhibit a defect in NF-kappa B regulation due to a hyperactive I kappa B kinase.  J Immunol. 2001;  167 1461-1468
  • 20 Poligone B, Weaver Jr DJ, Sen P, Baldwin Jr AS, Tisch R. Elevated NF-kappaB activation in nonobese diabetic mouse dendritic cells results in enhanced APC function.  J Immunol. 2002;  168 188-196
  • 21 Takahashi K, Honeyman MC, Harrison LC. Impaired yield, phenotype, and function of monocyte-derived dendritic cells in humans at risk for insulin-dependent diabetes.  J Immun. 1998;  161 2629-2635
  • 22 Summers KL, Marleau AM, Mahon JL, MacManus R, Hramiak I, Singh B. Reduced IFN-alpha secretion by blood dendritic cells in human diabetes.  Clin Immun. 2006;  121 81-89
  • 23 Peng R, Li Y, Brezner K, Litherland S, Clare-Salzler MJ. Abnormal peripheral blood dendritic cell populations in type 1 diabetes.  Ann N Y Acad Sci. 2003;  1005 222-225
  • 24 Teig N, Moses D, Gieseler S, Schauer U. Age-related changes in human blood dendritic cell subpopulations.  Scand J Immunol. 2002;  55 453-457
  • 25 Spatz M, Eibl N, Hink S, Wolf HM, Fischer GF, Mayr WR, Schernthaner G, Eibl MM. Impaired primary immune response in type-1 diabetes. Functional impairment at the level of APCs and T-cells.  Cell Immunol. 2003;  221 15-26
  • 26 Pickl WF, Majdic O, Kohl P, Stockl J, Riedl E, Scheinecker C, Bello-Fernandez C, Knapp W. Molecular and functional characteristics of dendritic cells generated from highly purified CD14+peripheral blood monocytes.  J Immunol. 1996;  157 3850-3859
  • 27 Jacobs B, Wuttke M, Papewalis C, Fenk R, Stüssgen C, Baehring T, Schinner S, Raffel A, Seissler J, Schott M. Characterization of Monocyte-derived IFNalpha-generated Dendritic Cells.  Horm Metab Res. 2008;  40 117-121
  • 28 Kadowaki N, Antonenko S, Lau JY, Liu YJ. Natural interferon alpha/beta-producing cells link innate and adaptive immunity.  J Exp Med. 2000;  192 219-226
  • 29 Cella M, Facchetti F, Lanzavecchia A, Colonna M. Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization.  Nat Immunol. 2000;  1 305-310
  • 30 Migita K, Miyashita T, Maeda Y, Kimura H, Nakamura M, Yatsuhashi H, Ishibashi H, Eguchi K. Reduced blood BDCA-2+(lymphoid) and CD11c+(myeloid) dendritic cells in systemic lupus erythematosus.  Clin Exp Immunol. 2005;  142 84-91
  • 31 Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahnsen FL. Plasmacytoid dendritic cells (natural interferon- alpha/beta-producing cells) accumulate in cutaneous lupus erythematosus lesions.  Am J Pathol. 2001;  159 237-243
  • 32 Cederblad B, Blomberg S, Vallin H, Perers A, Alm GV, Ronnblom L. Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-alpha- producing cells.  J Autoimmun. 1998;  11 465-470
  • 33 Palucka AK, Banchereau J, Blanco P, Pascual V. The interplay of dendritic cell subsets in systemic lupus erythematosus.  Immunol Cell Biol. 2002;  80 484-488
  • 34 Piemonti L, Leone BE, Nano R, Saccani A, Monti P, Maffi P, Bianchi G, Sica A, Peri G, Melzi R, Aldrighetti L, Secchi A, Carlo V Di, Allavena P, Bertuzzi F. Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation.  Diabetes. 2002;  51 55-65
  • 35 Saxena V, Ondr JK, Magnusen AF, Munn DH, Katz JD. The countervailing actions of myeloid and plasmacytoid dendritic cells control autoimmune diabetes in the nonobese diabetic mouse.  J Immunol. 2007;  179 5041-5053
  • 36 Seifarth C, Hinkmann C, Hahn EG, Lohmann T, Harsch IA. Reduced frequency of peripheral dendritic cells in type 2 diabetes.  Exp Clin Endocrinol Diabetes. 2008;  116 162-166

1 Current address: Medizinische Klinik, Städtisches Krankenhaus Dresden-Neustadt, Dresden, Germany

Correspondence

PD Dr. med. C. C. Seifarth

Dr.-Dachs-Straße 12

93049 Regensburg

Germany

Phone: +49/700/4676 66 33

Fax: +49/941/598 93 08

Email: seifarth@hotmail.com