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Published in: Immunologic Research 1/2019

Open Access 01-02-2019 | Type 1 Diabetes | ORIGINAL ARTICLE

Putative loss of CD83 immunosuppressive activity in long-standing complication-free juvenile diabetic patients during disease progression

Authors: Ulana Juhas, Monika Ryba-Stanisławowska, Urszula Ławrynowicz, Małgorzata Myśliwiec, Jolanta Myśliwska

Published in: Immunologic Research | Issue 1/2019

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Abstract

The CD83 molecule is a known marker of dendritic cell differentiation process, and its soluble form (sCD83) exerts immunosuppressive functions. In our research, we examined whether the sCD83 plasma concentration is impaired in DM1 children and if the expected changes are in line with the disturbed process of monocyte’s transformation into mCD83+ monocyte-derived cells. 28 newly diagnosed (ND-DM1) and 30 long-standing (LS-DM1) patients were enrolled into our study. We revealed that the examined cells show a high mCD83 expression level in ND-DM1, which was significantly downregulated by the TNF-α stimulation. The results were in line with those from healthy controls. We also observed that monocyte differentiation process into CD83+ cells was much defective in LS-DM1 children and the mCD83 expression level seems not to be controlled by TNF-α. Moreover, the sCD83 level was significantly decreased in plasma from LS-DM1 children and it was negatively related to HbA1c levels, while no correlations were observed between TNF-α plasma concentration or disease duration. Summarizing, our results suggest that reduced sCD83 levels may correspond with a poor metabolic control in LS-DM1 patients and therapeutic administration of this molecule may indicate a new therapy approach in the chronic phase of diabetes.
Literature
2.
go back to reference Alexandraki KI, Piperi C, Ziakas PD, Apostolopoulos NV, Makrilakis K, Syriou V, et al. Cytokine secretion in long-standing diabetes mellitus type 1 and 2: associations with low-grade systemic inflammation. J Clin Immunol. 2008;28:314–21.CrossRefPubMed Alexandraki KI, Piperi C, Ziakas PD, Apostolopoulos NV, Makrilakis K, Syriou V, et al. Cytokine secretion in long-standing diabetes mellitus type 1 and 2: associations with low-grade systemic inflammation. J Clin Immunol. 2008;28:314–21.CrossRefPubMed
3.
go back to reference Navarro-González JF, Mora-Fernández C, Muros de Fuentes M, García-Pérez J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol. 2011;7:327–740.CrossRefPubMed Navarro-González JF, Mora-Fernández C, Muros de Fuentes M, García-Pérez J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol. 2011;7:327–740.CrossRefPubMed
4.
go back to reference Rangasamy S, McGuire PG, Franco Nitta C, Monickaraj F, Oruganti SR, Das A. Chemokine mediated monocyte trafficking into the retina: role of inflammation in alteration of the blood-retinal barrier in diabeticretinopathy. PLoS One. 2014;20(9):e108508.CrossRef Rangasamy S, McGuire PG, Franco Nitta C, Monickaraj F, Oruganti SR, Das A. Chemokine mediated monocyte trafficking into the retina: role of inflammation in alteration of the blood-retinal barrier in diabeticretinopathy. PLoS One. 2014;20(9):e108508.CrossRef
5.
go back to reference Myśliwska J, Smardzewski M, Marek-Trzonkowska N, Myśliwiec M, Raczyńska K. Expansion of CD14+CD16+ monocytes producing TNF-α in complication-free diabetes type 1 juvenile onset patients. Cytokine. 2012;60:309–17.CrossRefPubMed Myśliwska J, Smardzewski M, Marek-Trzonkowska N, Myśliwiec M, Raczyńska K. Expansion of CD14+CD16+ monocytes producing TNF-α in complication-free diabetes type 1 juvenile onset patients. Cytokine. 2012;60:309–17.CrossRefPubMed
6.
go back to reference Ryba-Stanisławowska M, Myśliwska J, Juhas U, Myśliwiec M. Elevated levels of peripheral blood CD14bright CD16+ and CD14dim CD16+ monocytes may contribute to the development of retinopathy in patients with juvenile onset type 1 diabetes. APMIS. 2015;123:793–9.CrossRefPubMed Ryba-Stanisławowska M, Myśliwska J, Juhas U, Myśliwiec M. Elevated levels of peripheral blood CD14bright CD16+ and CD14dim CD16+ monocytes may contribute to the development of retinopathy in patients with juvenile onset type 1 diabetes. APMIS. 2015;123:793–9.CrossRefPubMed
7.
go back to reference Belge KU, Dayyani F, Horelt A, Siedlar M, Frankenberger M, Frankenberger B, et al. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J Immunol. 2002;168:3536–42.CrossRefPubMed Belge KU, Dayyani F, Horelt A, Siedlar M, Frankenberger M, Frankenberger B, et al. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J Immunol. 2002;168:3536–42.CrossRefPubMed
8.
go back to reference Zorena K, Myśliwska J, Myśliwiec M, Balcerska A, Hak Ł, Lipowski P, et al. Serum TNF-alpha level predicts nonproliferative diabetic retinopathy in children. Mediat Inflamm. 2007;2007:92196.CrossRef Zorena K, Myśliwska J, Myśliwiec M, Balcerska A, Hak Ł, Lipowski P, et al. Serum TNF-alpha level predicts nonproliferative diabetic retinopathy in children. Mediat Inflamm. 2007;2007:92196.CrossRef
9.
go back to reference Schram MT, Chaturvedi N, Schalkwijk C, Giorgino F, Ebeling P, Fuller JH, et al. Vascular risk factors and markers of endothelial function as determinants of inflammatory markers in type 1 diabetes. Diabetes Care. 2003;26:2165–73.CrossRefPubMed Schram MT, Chaturvedi N, Schalkwijk C, Giorgino F, Ebeling P, Fuller JH, et al. Vascular risk factors and markers of endothelial function as determinants of inflammatory markers in type 1 diabetes. Diabetes Care. 2003;26:2165–73.CrossRefPubMed
10.
go back to reference Myśliwiec M, Balcerska A, Zorena K, Kamińska H, Nowacka M, Sibińska Ż, et al. Relationship between the level of TNFα, IL6 and risk of renal proximal tubules damage in children with newly diagnosed diabetes mellitus type 1. Pol J Environ Stud. 2005;14:292–5. Myśliwiec M, Balcerska A, Zorena K, Kamińska H, Nowacka M, Sibińska Ż, et al. Relationship between the level of TNFα, IL6 and risk of renal proximal tubules damage in children with newly diagnosed diabetes mellitus type 1. Pol J Environ Stud. 2005;14:292–5.
11.
go back to reference Mysliwiec M, Zorena K, Balcerska A, Mysliwska J. Does tumor necrosis factor-α preceed occurrence of microalbuminuria in type 1 diabetes mellitus children? J Polish Diabetol Assoc. 2006;3:131–6. Mysliwiec M, Zorena K, Balcerska A, Mysliwska J. Does tumor necrosis factor-α preceed occurrence of microalbuminuria in type 1 diabetes mellitus children? J Polish Diabetol Assoc. 2006;3:131–6.
13.
go back to reference Lutz MB, Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol. 2002;23:445–9.CrossRefPubMed Lutz MB, Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol. 2002;23:445–9.CrossRefPubMed
14.
go back to reference Zhou LJ, Tedder TF. Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. J Immunol. 1995;154:3821–35.PubMed Zhou LJ, Tedder TF. Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. J Immunol. 1995;154:3821–35.PubMed
15.
go back to reference Zhou LJ, Schwarting R, Smith HM, Tedder TF. A novel cell-surface molecule expressed by human interdigitating reticulum cells, Langerhans cells, and activated lymphocytes is a new member of the Ig superfamily. J Immunol. 1992;149:735.PubMed Zhou LJ, Schwarting R, Smith HM, Tedder TF. A novel cell-surface molecule expressed by human interdigitating reticulum cells, Langerhans cells, and activated lymphocytes is a new member of the Ig superfamily. J Immunol. 1992;149:735.PubMed
16.
go back to reference Gregori S, Tomasoni D, Pacciani V, Scirpoli M, Battaglia M, Magnani CF, et al. Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway. Blood. 2010;116:935–44.CrossRefPubMed Gregori S, Tomasoni D, Pacciani V, Scirpoli M, Battaglia M, Magnani CF, et al. Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway. Blood. 2010;116:935–44.CrossRefPubMed
17.
go back to reference Hock BD, Kato M, McKenzie JL, Hart DN. A soluble form of CD83 is released from activated dendritic cells and B lymphocytes, and is detectable in normal human sera. Int Immunol. 2001;13:959–67.CrossRefPubMed Hock BD, Kato M, McKenzie JL, Hart DN. A soluble form of CD83 is released from activated dendritic cells and B lymphocytes, and is detectable in normal human sera. Int Immunol. 2001;13:959–67.CrossRefPubMed
18.
go back to reference Yamashiro S, Wang JM, Yang D, Gong WH, Kamohara H, Yoshimura T. Expression of CCR6 and CD83 by cytokine-activated human neutrophils. Blood. 2000;96:3958–63.PubMed Yamashiro S, Wang JM, Yang D, Gong WH, Kamohara H, Yoshimura T. Expression of CCR6 and CD83 by cytokine-activated human neutrophils. Blood. 2000;96:3958–63.PubMed
19.
20.
go back to reference Wolenski M, Cramer SO, Ehrlich S, Steeg C, Fleischer B, von Bonin A. Enhanced activation of CD83-positive T cells. Scand J Immunol. 2003;58:306–11.CrossRefPubMed Wolenski M, Cramer SO, Ehrlich S, Steeg C, Fleischer B, von Bonin A. Enhanced activation of CD83-positive T cells. Scand J Immunol. 2003;58:306–11.CrossRefPubMed
21.
go back to reference Ju X, Silveira PA, Hsu WH, Elgundi Z, Alingcastre R, Verma ND, et al. The analysis of CD83 expression on human immune cells identifies a unique CD83+-activated T cell population. J Immunol. 2016;197:4613–25.CrossRefPubMed Ju X, Silveira PA, Hsu WH, Elgundi Z, Alingcastre R, Verma ND, et al. The analysis of CD83 expression on human immune cells identifies a unique CD83+-activated T cell population. J Immunol. 2016;197:4613–25.CrossRefPubMed
22.
go back to reference Doebbeler M, Koenig C, Krzyzak L, Seitz C, Wild A, Ulas T, et al. CD83 expression is essential for Treg cell differentiation and stability. JCI Insight. 2018;3:99712.CrossRefPubMed Doebbeler M, Koenig C, Krzyzak L, Seitz C, Wild A, Ulas T, et al. CD83 expression is essential for Treg cell differentiation and stability. JCI Insight. 2018;3:99712.CrossRefPubMed
23.
go back to reference Fujimoto Y, Tu L, Miller AS, Bock C, Fujimoto M, Doyle C, et al. CD83 expression influences CD4+ T cell development in the thymus. Cell. 2002;108:755–67.CrossRefPubMed Fujimoto Y, Tu L, Miller AS, Bock C, Fujimoto M, Doyle C, et al. CD83 expression influences CD4+ T cell development in the thymus. Cell. 2002;108:755–67.CrossRefPubMed
24.
go back to reference Cao W, Lee SH, Lu J. CD83 is preformed inside monocytes, macrophages and dendritic cells, but it is only stably expressed on activated dendritic cells. Biochem J. 2005;385:85–93.CrossRefPubMed Cao W, Lee SH, Lu J. CD83 is preformed inside monocytes, macrophages and dendritic cells, but it is only stably expressed on activated dendritic cells. Biochem J. 2005;385:85–93.CrossRefPubMed
25.
go back to reference Lundell AC, Adlerberth I, Lindberg E, Karlsson H, Ekberg S, Aberg N, et al. Increased levels of circulating soluble CD14 but not CD83 in infants are associated with early intestinal colonization with Staphylococcus aureus. Clin Exp Allergy. 2007;37:62–71.CrossRefPubMed Lundell AC, Adlerberth I, Lindberg E, Karlsson H, Ekberg S, Aberg N, et al. Increased levels of circulating soluble CD14 but not CD83 in infants are associated with early intestinal colonization with Staphylococcus aureus. Clin Exp Allergy. 2007;37:62–71.CrossRefPubMed
26.
go back to reference Kristensen AM, Stengaard-Pedersen K, Hetland ML, Hørslev-Petersen K, Junker P, Østergaard M, et al. Expression of soluble CD83 in plasma from early-stage rheumatoid arthritis patients is not modified by anti-TNF-α therapy. Cytokine. 2017;96:1–7.CrossRefPubMed Kristensen AM, Stengaard-Pedersen K, Hetland ML, Hørslev-Petersen K, Junker P, Østergaard M, et al. Expression of soluble CD83 in plasma from early-stage rheumatoid arthritis patients is not modified by anti-TNF-α therapy. Cytokine. 2017;96:1–7.CrossRefPubMed
27.
go back to reference Hock BD, O’Donnell JL, Taylor K, Steinkasserer A, McKenzie JL, Rothwell AG, et al. Levels of the soluble forms of CD80, CD86, and CD83 are elevated in the synovial fluid of rheumatoid arthritis patients. Tissue Antigens. 2006;67:57–60.CrossRefPubMed Hock BD, O’Donnell JL, Taylor K, Steinkasserer A, McKenzie JL, Rothwell AG, et al. Levels of the soluble forms of CD80, CD86, and CD83 are elevated in the synovial fluid of rheumatoid arthritis patients. Tissue Antigens. 2006;67:57–60.CrossRefPubMed
28.
go back to reference Hock BD, Haring LF, Steinkasserer A, Taylor KG, Patton WN, McKenzie JL. The soluble form of CD83 is present at elevated levels in a number of hematological malignancies. Leuk Res. 2004;28:237–41.CrossRefPubMed Hock BD, Haring LF, Steinkasserer A, Taylor KG, Patton WN, McKenzie JL. The soluble form of CD83 is present at elevated levels in a number of hematological malignancies. Leuk Res. 2004;28:237–41.CrossRefPubMed
29.
go back to reference Karampoor S, Zahednasab H, Etemadifar M, Keyvani H. The levels of soluble forms of CD21 and CD83 in multiple sclerosis. J Neuroimmunol. 2018;320:11–4.CrossRefPubMed Karampoor S, Zahednasab H, Etemadifar M, Keyvani H. The levels of soluble forms of CD21 and CD83 in multiple sclerosis. J Neuroimmunol. 2018;320:11–4.CrossRefPubMed
30.
go back to reference Rabinovitch A. Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM. Therapeutic intervention by immunostimulation? Diabetes. 1994;43:613–21.CrossRefPubMed Rabinovitch A. Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM. Therapeutic intervention by immunostimulation? Diabetes. 1994;43:613–21.CrossRefPubMed
31.
go back to reference Stechova K, Bohmova K, Vrabelova Z, Sepa A, Stadlerova G, Zacharovova K, et al. High T-helper-1 cytokines but low T-helper-3 cytokines, inflammatory cytokines and chemokines in children with high risk of developing type 1 diabetes. Diabetes Metab Res Rev. 2007;23:462–71.CrossRefPubMed Stechova K, Bohmova K, Vrabelova Z, Sepa A, Stadlerova G, Zacharovova K, et al. High T-helper-1 cytokines but low T-helper-3 cytokines, inflammatory cytokines and chemokines in children with high risk of developing type 1 diabetes. Diabetes Metab Res Rev. 2007;23:462–71.CrossRefPubMed
32.
go back to reference Alnek K, Kisand K, Heilman K, Peet A, Varik K, Uibo R. Increased blood levels of growth factors, proinflammatory cytokines and Th17 cytokines in patients with newly diagnosed type 1 diabetes. PLoS One. 2015;10:e0142976.CrossRefPubMedPubMedCentral Alnek K, Kisand K, Heilman K, Peet A, Varik K, Uibo R. Increased blood levels of growth factors, proinflammatory cytokines and Th17 cytokines in patients with newly diagnosed type 1 diabetes. PLoS One. 2015;10:e0142976.CrossRefPubMedPubMedCentral
33.
go back to reference Horvatinovich JM, Grogan EW, Norris M, Steinkasserer A, Lemos H, Mellor AL, et al. Soluble CD83 inhibits T cell activation by binding to the TLR4/MD-2 complex on CD14+ monocytes. J Immunol. 2017;198:2286–301.CrossRefPubMedPubMedCentral Horvatinovich JM, Grogan EW, Norris M, Steinkasserer A, Lemos H, Mellor AL, et al. Soluble CD83 inhibits T cell activation by binding to the TLR4/MD-2 complex on CD14+ monocytes. J Immunol. 2017;198:2286–301.CrossRefPubMedPubMedCentral
34.
go back to reference Zinser E, Lechmann M, Golka A, Lutz MB, Steinkasserer A. Prevention and treatment of experimental autoimmune encephalomyelitis by soluble CD83. J Exp Med. 2004;200:345–51.CrossRefPubMedPubMedCentral Zinser E, Lechmann M, Golka A, Lutz MB, Steinkasserer A. Prevention and treatment of experimental autoimmune encephalomyelitis by soluble CD83. J Exp Med. 2004;200:345–51.CrossRefPubMedPubMedCentral
35.
go back to reference Ge W, Arp J, Lian D, Liu W, Baroja ML, Jiang J, et al. Immunosuppression involving soluble CD83 induces tolerogenic dendritic cells that prevent cardiacallograft rejection. Transplantation. 2010;90:1145–56.CrossRefPubMed Ge W, Arp J, Lian D, Liu W, Baroja ML, Jiang J, et al. Immunosuppression involving soluble CD83 induces tolerogenic dendritic cells that prevent cardiacallograft rejection. Transplantation. 2010;90:1145–56.CrossRefPubMed
36.
go back to reference Bock F, Rössner S, Onderka J, Lechmann M, Pallotta MT, Fallarino F, et al. Topical application of soluble CD83 induces IDO-mediated immune modulation, increases Foxp3+ T cells, and prolongs allogeneic corneal graft survival. J Immunol. 2013;191:1965–75.CrossRefPubMed Bock F, Rössner S, Onderka J, Lechmann M, Pallotta MT, Fallarino F, et al. Topical application of soluble CD83 induces IDO-mediated immune modulation, increases Foxp3+ T cells, and prolongs allogeneic corneal graft survival. J Immunol. 2013;191:1965–75.CrossRefPubMed
37.
go back to reference Sénéchal B, Boruchov AM, Reagan JL, Hart DN, Young JW. Infection of mature monocyte-derived dendritic cells with human cytomegalovirus inhibits stimulation of T-cell proliferation via the release of soluble CD83. Blood. 2004;103:4207–15.CrossRefPubMed Sénéchal B, Boruchov AM, Reagan JL, Hart DN, Young JW. Infection of mature monocyte-derived dendritic cells with human cytomegalovirus inhibits stimulation of T-cell proliferation via the release of soluble CD83. Blood. 2004;103:4207–15.CrossRefPubMed
38.
go back to reference Chen L, Zhu Y, Zhang G, Gao C, Zhong W, Zhang X. CD83-stimulated monocytes suppress T-cell immune responses through production of prostaglandin E2. Proc Natl Acad Sci U S A. 2011;108:18778–83.CrossRefPubMedPubMedCentral Chen L, Zhu Y, Zhang G, Gao C, Zhong W, Zhang X. CD83-stimulated monocytes suppress T-cell immune responses through production of prostaglandin E2. Proc Natl Acad Sci U S A. 2011;108:18778–83.CrossRefPubMedPubMedCentral
Metadata
Title
Putative loss of CD83 immunosuppressive activity in long-standing complication-free juvenile diabetic patients during disease progression
Authors
Ulana Juhas
Monika Ryba-Stanisławowska
Urszula Ławrynowicz
Małgorzata Myśliwiec
Jolanta Myśliwska
Publication date
01-02-2019
Publisher
Springer US
Keyword
Type 1 Diabetes
Published in
Immunologic Research / Issue 1/2019
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-019-09074-y

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