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Diabetologia
Erschienen in: Diabetologia 2/2005

01.02.2005 | Article

A functional CD40 receptor is expressed in pancreatic beta cells

verfasst von: D. Klein, F. Barbé-Tuana, A. Pugliese, H. Ichii, D. Garza, M. Gonzalez, R. D. Molano, C. Ricordi, R. L. Pastori

Erschienen in: Diabetologia | Ausgabe 2/2005

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Abstract

Aims/hypothesis

Despite differences in function and embryonic origin, pancreatic islet cells and neurons express proteins belonging to the tumour necrosis factor receptor superfamily. While neurons express the CD40 receptor, it is unknown whether islet cells also express it. We investigated CD40 expression in human and mouse pancreatic islets as well as in NIT-1 insulinoma cells.

Methods

CD40 expression was studied by reverse transcriptase polymerase chain reaction, flow cytometry, immunohistochemistry and western blot. Responses mediated by CD40 were assessed by a luciferase gene reporter assay following stimulation with a CD40 agonist antibody.

Results

We found that CD40 is expressed in mouse and human pancreatic islet cells. CD40 is expressed by beta cells, and its expression is upregulated by proinflammatory cytokines (IL-1β, IFN-γ and TNF-α). CD40 signalling in NIT-1 insulinoma cells activates nuclear factor kappa-B, demonstrating that CD40 is functional.

Conclusions/interpretation

We present evidence that, in addition to immune cell types, mouse and human pancreatic beta cells express CD40. Its expression is upregulated by proinflammatory stimuli, and signalling through this receptor activates NF-κB. We suggest that the effects of inflammatory stimuli that affect beta cell function and survival may be also mediated by signalling through the CD40 receptor. Thus, CD40 may have a role in processes associated with islet autoimmunity and transplantation.
Literatur
1.
Stamenkovic I, Clark EA, Seed B (1989) A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas. EMBO J 8:1403–1410
2.
Hollenbaugh D, Grosmaire LS, Kullas CD et al (1992) The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity. EMBO J 11:4313–4321
3.
Armitage RJ, Fanslow WC, Strockbine L et al (1992) Molecular and biological characterization of a murine ligand for CD40. Nature 357:80–82
4.
Grewal IS, Flavell RA (1998) CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 16:111–135
5.
Klaus SJ, Berberich I, Shu G, Clark EA (1994) CD40 and its ligand in the regulation of humoral immunity. Semin Immunol 6:279–286
6.
Yang Y, Wilson JM (1996) CD40 ligand-dependent T cell activation: requirement of B7-CD28 signaling through CD40. Science 273:1862–1864
7.
Lenschow DJ, Walunas TL, Bluestone JA (1996) CD28/B7 system of T cell costimulation. Annu Rev Immunol 14:233–258PubMed
8.
Larsen CP, Alexander DZ, Hollenbaugh D et al (1996) CD40-gp39 interactions play a critical role during allograft rejection: suppression of allograft rejection by blockade of the CD40-gp39 pathway. Transplantation 61:4–9
9.
Parker DC, Greiner DL, Phillips NE et al (1995) Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and antibody to CD40 ligand. Proc Natl Acad Sci U S A 92:9560–9564
10.
Kirk AD, Harlan DM, Armstrong NN et al (1997) CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc Natl Acad Sci U S A 94:8789–8794
11.
Kenyon NS, Chatzipetrou M, Masetti M et al (1999) Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154. Proc Natl Acad Sci U S A 96:8132–8137
12.
Mohan C, Shi Y, Laman JD, Datta SK (1995) Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis. J Immunol 154:1470–1480
13.
Balasa B, Krahl T, Patstone G et al (1997) CD40 ligand–CD40 interactions are necessary for the initiation of insulitis and diabetes in nonobese diabetic mice. J Immunol 159:4620–4627
14.
van Kooten C, Banchereau J (2000) CD40–CD40 ligand. J Leukoc Biol 67:2–17
15.
Calderhead DM, Kosaka Y, Manning EM, Noelle RJ (2000) CD40–CD154 interactions in B-cell signaling. Curr Top Microbiol Immunol 245:73–99
16.
Rathmell JC, Townsend SE, Xu JC, Flavell RA, Goodnow CC (1996) Expansion or elimination of B cells in vivo: dual roles for CD40- and Fas (CD95)-ligands modulated by the B cell antigen receptor. Cell 87:319–329
17.
Wagner DH Jr, Vaitaitis G, Sanderson R, Poulin M, Dobbs C, Haskins K (2002) Expression of CD40 identifies a unique pathogenic T cell population in type 1 diabetes. Proc Natl Acad Sci U S A 99:3782–3787
18.
Karmann K, Hughes CC, Schechner J, Fanslow WC, Pober JS (1995) CD40 on human endothelial cells: inducibility by cytokines and functional regulation of adhesion molecule expression. Proc Natl Acad Sci U S A 92:4342–4346
19.
Galy AH, Spits H (1992) CD40 is functionally expressed on human thymic epithelial cells. J Immunol 149:775–782
20.
Tan J, Town T, Mori T et al (2002) CD40 is expressed and functional on neuronal cells. EMBO J 21:643–652
21.
Smith TJ, Sciaky D, Phipps RP, Jennings TA (1999) CD40 expression in human thyroid tissue: evidence for involvement of multiple cell types in autoimmune and neoplastic diseases. Thyroid 9:749–755
22.
Sugimoto K, Shiraki K, Ito T et al (1999) Expression of functional CD40 in human hepatocellular carcinoma. Hepatology 30:920–926
23.
Hess S, Engelmann H (1996) A novel function of CD40: induction of cell death in transformed cells. J Exp Med 183:159–167
24.
Vosters O, Beuneu C, Nagy N et al (2004) CD40 expression on human pancreatic duct cells: role in nuclear factor-kappa B activation and production of pro-inflammatory cytokines. Diabetologia 47:660–668
25.
Ghia P, Boussiotis VA, Schultze JL et al (1998) Unbalanced expression of bcl-2 family proteins in follicular lymphoma: contribution of CD40 signaling in promoting survival. Blood 91:244–251
26.
Hess S, Gottfried E, Smola H, Grunwald U, Schuchmann M, Engelmann H (1998) CD40 induces resistance to TNF-mediated apoptosis in a fibroblast cell line. Eur J Immunol 28:3594–3604
27.
Wingett DG, Vestal RE, Forcier K, Hadjokas N, Nielson CP (1998) CD40 is functionally expressed on human breast carcinomas: variable inducibility by cytokines and enhancement of Fas-mediated apoptosis. Breast Cancer Res Treat 50:27–36
28.
Gallagher NJ, Eliopoulos AG, Agathangelo A, Oates J, Crocker J, Young LS (2002) CD40 activation in epithelial ovarian carcinoma cells modulates growth, apoptosis, and cytokine secretion. Mol Pathol 55:110–120
29.
Nadeau S, Rivest S (1999) Effects of circulating tumor necrosis factor on the neuronal activity and expression of the genes encoding the tumor necrosis factor receptors (p55 and p75) in the rat brain: a view from the blood-brain barrier. Neuroscience 93:1449–1464
30.
Chao MV (1994) The p75 neurotrophin receptor. J Neurobiol 25:1373–1385
31.
Stephens LA, Thomas HE, Ming L et al (1999) Tumor necrosis factor-alpha-activated cell death pathways in NIT-1 insulinoma cells and primary pancreatic beta cells. Endocrinology 140:3219–3227
32.
Kanaka-Gantenbein C, Dicou E, Czernichow P, Scharfmann R (1995) Presence of nerve growth factor and its receptors in an in vitro model of islet cell development: implication in normal islet morphogenesis. Endocrinology 136:3154–3162
33.
Scharfmann R, Tazi A, Polak M, Kanaka C, Czernichow P (1993) Expression of functional nerve growth factor receptors in pancreatic beta-cell lines and fetal rat islets in primary culture. Diabetes 42:1829–1836
34.
Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW (1988) Automated method for isolation of human pancreatic islets. Diabetes 37:413–420
35.
Bottino R, Fernandez LA, Ricordi C et al (1998) Transplantation of allogeneic islets of Langerhans in the rat liver: effects of macrophage depletion on graft survival and microenvironment activation. Diabetes 47:316–323
36.
Lukowiak B, Vandewalle B, Riachy R et al (2001) Identification and purification of functional human beta-cells by a new specific zinc-fluorescent probe. J Histochem Cytochem 49:519–528
37.
Toyoda H, Formby B, Magalong D et al (1994) In situ islet cytokine gene expression during development of type I diabetes in the non-obese diabetic mouse. Immunol Lett 39:283–288
38.
Eizirik DL, Mandrup-Poulsen T (2001) A choice of death—the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 44:2115–2133CrossRefPubMed
39.
Cardozo AK, Heimberg H, Heremans Y et al (2001) A comprehensive analysis of cytokine-induced and nuclear factor-kappa B-dependent genes in primary rat pancreatic beta-cells. J Biol Chem 276:48879–48886CrossRefPubMed
40.
Wong S, Guerder S, Visintin I et al (1995) Expression of the co-stimulator molecule B7-1 in pancreatic beta-cells accelerates diabetes in the NOD mouse. Diabetes 44:326–329
41.
Wong FS, Visintin I, Wen L, Granata J, Flavell R, Janeway CA (1998) The role of lymphocyte subsets in accelerated diabetes in nonobese diabetic-rat insulin promoter-B7-1 (NOD-RIP-B7-1) mice. J Exp Med 187:1985–1993
42.
Harlan DM, Hengartner H, Huang ML et al (1994) Mice expressing both B7-1 and viral glycoprotein on pancreatic beta cells along with glycoprotein-specific transgenic T cells develop diabetes due to a breakdown of T-lymphocyte unresponsiveness. Proc Natl Acad Sci U S A 91:3137–3141
43.
Wen L, Wong FS, Tang J et al (2000) In vivo evidence for the contribution of human histocompatibility leukocyte antigen (HLA)-DQ molecules to the development of diabetes. J Exp Med 191:97–104
44.
Phillips NE, Markees TG, Mordes JP, Greiner DL, Rossini AA (2003) Blockade of CD40-mediated signaling is sufficient for inducing islet but not skin transplantation tolerance. J Immunol 170:3015–3023
45.
Kawabe T, Naka T, Yoshida K et al (1994) The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation. Immunity 1:167–178
Metadaten
Titel
A functional CD40 receptor is expressed in pancreatic beta cells
verfasst von
D. Klein
F. Barbé-Tuana
A. Pugliese
H. Ichii
D. Garza
M. Gonzalez
R. D. Molano
C. Ricordi
R. L. Pastori
Publikationsdatum
01.02.2005
Erschienen in
Diabetologia / Ausgabe 2/2005
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1645-7

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