Comparison of morphology, phenotypes and function between cultured human IL‑4‑DC and IFN‑DC

Jin,Zhiliang; Fan,Jing; Zhang,Yajuan; Yi,Yongxiang; Wang,Lili; Yin,Dandan; Deng,Tao; Ye,Wei

doi:10.3892/mmr.2017.7581

Comparison of morphology, phenotypes and function between cultured human IL‑4‑DC and IFN‑DC

Authors:
- Zhiliang Jin
- Jing Fan
- Yajuan Zhang
- Yongxiang Yi
- Lili Wang
- Dandan Yin
- Tao Deng
- Wei Ye
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Affiliations: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, P.R. China, Cancer Research and Biotherapy Center, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, Jiangsu 210003, P.R. China, Health Management Center, Danyang People's Hospital, Zhenjiang, Jiangsu 210003, P.R. China
Published online on: September 21, 2017 https://doi.org/10.3892/mmr.2017.7581
Pages: 7345-7354
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dendritic cells (DCs) as professional antigen presenting cells, are important in the initiation of the primary immune response. The present study compared the morphology, phenotypes and function between monocyte‑derived human DCs produced from a conventional culturing system containing granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) and IL‑4 (IL‑4‑DC) and DCs generated by the stimulation of GM‑CSF and interferon (IFN)‑α (IFN‑DC). When compared with IL‑4‑DC in morphology, IFN‑DC contained more organelles, including endoplasmic reticulum and myelin figures, whereas mature (m)IL‑4‑DC contained more vacuoles in the cells. The spikes of IFN‑DC were shorter and thicker. The expression of phenotypes between immature IFN‑DC and IL‑4‑DC were diverse. Following maturation with tumor necrosis factor‑α, IFN‑DC and IL‑4‑DC upregulated the expression of cluster of differentiation (CD) 11c and CD83. Conversely, immature IFN‑DC and IL‑4‑DC secreted few inflammatory cytokines including interleukin (IL)‑18, IL‑23, IL‑12p70, IL‑1β and anti‑inflammatory IL‑10. Following maturation, large amounts of the cytokines were secreted by these two DCs and mIFN‑DC secreted more cytokines compared with mIL‑4‑DC in general. Furthermore, immature IFN‑DC and IL‑4‑DC loaded with cytomegalovirus (CMV)‑pp65 protein were unable to induce the priming of T cells, as evaluated by the intracellular staining with IFN‑γ. Notably, mature DCs exhibited the ability to present CMV‑pp65 protein and activate T cells. The mIFN‑DC activated a greater proportion of autologous CD4+ T cells (0.91 vs. 0.31%, P<0.001) and CD8+ T cells (0.90 vs. 0.48%, P<0.001) to secret IFN‑γ compared with mIL‑4‑DC. The results suggested that the morphology, phenotypes and cytokine secretion of IFN‑DC and IL‑4‑DC were diverse. The mIFN‑DC were more effective in priming and cross‑priming T cells when compared with IL‑4‑DC.

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1	Mohty M, Vialle-Castellano A, Nunes JA, Isnardon D, Olive D and Gaugler B: IFN-alpha skews monocyte differentiation into Toll-like receptor 7-expressing dendritic cells with potent functional activities. J Immunol. 171:3385–3393. 2003. View Article : Google Scholar : PubMed/NCBI
2	van Montfoort N, van der Aa E and Woltman AM: Understanding MHC class I presentation of viral antigens by human dendritic cells as a basis for rational design of therapeutic vaccines. Front Immunol. 5:1822014. View Article : Google Scholar : PubMed/NCBI
3	Schreibelt G, Klinkenberg LJ, Cruz LJ, Tacken PJ, Tel J, Kreutz M, Adema GJ, Brown GD, Figdor CG and de Vries IJ: The C-type lectin receptor CLEC9A mediates antigen uptake and (cross-)presentation by human blood BDCA3⁺ myeloid dendritic cells. Blood. 119:2284–2292. 2012. View Article : Google Scholar : PubMed/NCBI
4	Sugita S, Kawazoe Y, Imai A, Usui Y, Iwakura Y, Isoda K, Ito M and Mochizuki M: Mature dendritic cell suppression by IL-1 receptor antagonist on retinal pigment epithelium cells. Invest Ophthalmol Vis Sci. 54:3240–3249. 2013. View Article : Google Scholar : PubMed/NCBI
5	Kim SW, Choi SM, Choo YS, Kim IK, Song BW and Kim HS: Flt3 ligand induces monocyte proliferation and enhances the function of monocyte-derived dendritic cells in vitro. J Cell Physiol. 230:1740–1749. 2015. View Article : Google Scholar : PubMed/NCBI
6	Gabriele L, Borghi P, Rozera C, Sestili P, Andreotti M, Guarini A, Montefusco E, Foà R and Belardelli F: IFN-alpha promotes the rapid differentiation of monocytes from patients with chronic myeloid leukemia into activated dendritic cells tuned to undergo full maturation after LPS treatment. Blood. 103:980–987. 2004. View Article : Google Scholar : PubMed/NCBI
7	Paquette RL, Hsu NC, Kiertscher SM, Park AN, Tran L, Roth MD and Glaspy JA: Interferon-alpha and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells. J Leukoc Biol. 64:358–367. 1998.PubMed/NCBI
8	Lapenta C, Santini SM, Logozzi M, Spada M, Andreotti M, Di Pucchio T, Parlato S and Belardelli F: Potent immune response against HIV-1 and protection from virus challenge in hu-PBL-SCID mice immunized with inactivated virus-pulsed dendritic cells generated in the presence of IFN-alpha. J Exp Med. 198:361–367. 2003. View Article : Google Scholar : PubMed/NCBI
9	Rizza P, Moretti F, Capone I and Belardelli F: Role of type I interferon in inducing a protective immune response: Perspectives for clinical applications. Cytokine Growth Factor Rev. 26:195–201. 2015. View Article : Google Scholar : PubMed/NCBI
10	Spadaro F, Lapenta C, Donati S, Abalsamo L, Barnaba V, Belardelli F, Santini SM and Ferrantini M: IFN-alpha enhances cross-presentation in human dendritic cells by modulating antigen survival, endocytic routing, and processing. Blood. 119:1407–1417. 2012. View Article : Google Scholar : PubMed/NCBI
11	Carbonneil C, Aouba A, Burgard M, Cardinaud S, Rouzioux C, Langlade-Demoyen P and Weiss L: Dendritic cells generated in the presence of granulocyte-macrophage colony-stimulating factor and IFN-alpha are potent inducers of HIV-specific CD8 T cells. AIDS. 17:1731–1740. 2003. View Article : Google Scholar : PubMed/NCBI
12	Lapenta C, Santini SM, Spada M, Donati S, Urbani F, Accapezzato D, Franceschini D, Andreotti M, Barnaba V and Belardelli F: IFN-alpha-conditioned dendritic cells are highly efficient in inducing cross-priming CD8(+) T cells against exogenous viral antigens. Eur J Immunol. 36:2046–2060. 2006. View Article : Google Scholar : PubMed/NCBI
13	Pilon C, Levast B, Meurens F, Le Vern Y, Kerboeuf D, Salmon H, Velge-Roussel F, Lebranchu Y and Baron C: CD40 engagement strongly induces CD25 expression on porcine dendritic cells and polarizes the T cell immune response toward Th1. Mol Immunol. 46:437–447. 2009. View Article : Google Scholar : PubMed/NCBI
14	Korthals M, Safaian N, Kronenwett R, Maihöfer D, Schott M, Papewalis C, Blanco E Diaz, Winter M, Czibere A, Haas R, et al: Monocyte derived dendritic cells generated by IFN-alpha acquire mature dendritic and natural killer cell properties as shown by gene expression analysis. J Transl Med. 5:462007. View Article : Google Scholar : PubMed/NCBI
15	McRae BL, Nagai T, Semnani RT, van Seventer JM and van Seventer GA: Interferon-alpha and -beta inhibit the in vitro differentiation of immunocompetent human dendritic cells from CD14(+) precursors. Blood. 96:210–217. 2000.PubMed/NCBI
16	Lapenta C, Donati S, Spadaro F, Castaldo P, Belardelli F, Cox MC and Santini SM: NK cell activation in the antitumor response induced by IFN-α dendritic cells loaded with apoptotic cells from follicular lymphoma patients. J Immunol. 197:795–806. 2016. View Article : Google Scholar : PubMed/NCBI
17	Chabot V, Martin L, Meley D, Sensebé L, Baron C, Lebranchu Y, Dehaut F and Velge-Roussel F: Unexpected impairment of TNF-α-induced maturation of human dendritic cells in vitro by IL-4. J Transl Med. 14:932016. View Article : Google Scholar : PubMed/NCBI
18	Farkas A, Tonel G and Nestle FO: Interferon-alpha and viral triggers promote functional maturation of human monocyte-derived dendritic cells. Br J Dermatol. 158:921–929. 2008. View Article : Google Scholar : PubMed/NCBI
19	Santini SM, Lapenta C, Donati S, Spadaro F, Belardelli F and Ferrantini M: Interferon-α-conditioned human monocytes combine a Th1-orienting attitude with the induction of autologous Th17 responses: Role of IL-23 and IL-12. PLoS One. 6:e173642011. View Article : Google Scholar : PubMed/NCBI
20	Trinchieri G: Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 3:133–146. 2003. View Article : Google Scholar : PubMed/NCBI
21	Askenase MH, Han SJ, Byrd AL, da Fonseca Morais D, Bouladoux N, Wilhelm C, Konkel JE, Hand TW, Lacerda-Queiroz N, Su XZ, et al: Bone-marrow-resident NK cells prime monocytes for regulatory function during infection. Immunity. 42:1130–1142. 2015. View Article : Google Scholar : PubMed/NCBI
22	Childs BG, Baker DJ, Wijshake T, Conover CA, Campisi J and van Deursen JM: Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science. 354:472–477. 2016. View Article : Google Scholar : PubMed/NCBI
23	Oehler L, Majdic O, Pickl WF, Stöckl J, Riedl E, Drach J, Rappersberger K, Geissler K and Knapp W: Neutrophil granulocyte-committed cells can be driven to acquire dendritic cell characteristics. J Exp Med. 187:1019–1028. 1998. View Article : Google Scholar : PubMed/NCBI
24	Farkas A and Kemény L: Interferon-α in the generation of monocyte-derived dendritic cells: recent advances and implications for dermatology. Br J Dermatol. 165:247–254. 2011. View Article : Google Scholar : PubMed/NCBI
25	Wang S, Sun X, Zhou H, Zhu Z, Zhao W and Zhu C: Interleukin-4 affects the mature phenotype and function of rat bone marrow-derived dendritic cells. Mol Med Rep. 12:233–237. 2015. View Article : Google Scholar : PubMed/NCBI
26	Gessani S, Conti L, Del Cornò M and Belardelli F: Type I interferons as regulators of human antigen presenting cell functions. Toxins (Basel). 6:1696–1723. 2014. View Article : Google Scholar : PubMed/NCBI
27	Guenova E, Skabytska Y, Hoetzenecker W, Weindl G, Sauer K, Tham M, Kim KW, Park JH, Seo JH, Ignatova D, et al: IL-4 abrogates T(H)17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells. Proc Natl Acad Sci USA. 112:2163–2168. 2015; View Article : Google Scholar : PubMed/NCBI
28	Okada S, Han S, Patel ES, Yang LJ and Chang LJ: STAT3 signaling contributes to the high effector activities of interleukin-15-derived dendritic cells. Immunol Cell Biol. 93:461–471. 2015. View Article : Google Scholar : PubMed/NCBI
29	Taieb A, Breitinger JJ, Unadkat JV, Shufesky WJ, Morelli AE, Thomson AW, Lee WP and Feili-Hariri M: Intrinsic ability of GM+IL-4 but not Flt3L-induced rat dendritic cells to promote allogeneic T cell hyporesponsiveness. Clin Immunol. 123:176–189. 2007. View Article : Google Scholar : PubMed/NCBI
30	Carbonneil C, Saidi H, Donkova-Petrini V and Weiss L: Dendritic cells generated in the presence of interferon-alpha stimulate allogeneic CD4⁺ T-cell proliferation: Modulation by autocrine IL-10, enhanced T-cell apoptosis and T regulatory type 1 cells. Int Immunol. 16:1037–1052. 2004. View Article : Google Scholar : PubMed/NCBI
31	Bella S Della, Nicola S, Riva A, Biasin M, Clerici M and Villa ML: Functional repertoire of dendritic cells generated in granulocyte macrophage-colony stimulating factor and interferon-alpha. J Leukoc Biol. 75:106–116. 2004. View Article : Google Scholar : PubMed/NCBI
32	Papewalis C, Jacobs B, Wuttke M, Ullrich E, Baehring T, Fenk R, Willenberg HS, Schinner S, Cohnen M, Seissler J, et al: IFN-alpha skews monocytes into CD56⁺-expressing dendritic cells with potent functional activities in vitro and in vivo. J Immunol. 180:1462–1470. 2008. View Article : Google Scholar : PubMed/NCBI
33	Fujii S, Liu K, Smith C, Bonito AJ and Steinman RM: The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J Exp Med. 199:1607–1618. 2004. View Article : Google Scholar : PubMed/NCBI
34	Freeman GJ, Gribben JG, Boussiotis VA, Ng JW, Restivo VA Jr, Lombard LA, Gray GS and Nadler LM: Cloning of B7-2: A CTLA-4 counter-receptor that costimulates human T cell proliferation. Science. 262:909–911. 1993. View Article : Google Scholar : PubMed/NCBI
35	Evans EJ, Esnouf RM, Manso-Sancho R, Gilbert RJ, James JR, Yu C, Fennelly JA, Vowles C, Hanke T, Walse B, et al: Crystal structure of a soluble CD28-Fab complex. Nat Immunol. 6:271–279. 2005. View Article : Google Scholar : PubMed/NCBI
36	Pentcheva-Hoang T, Egen JG, Wojnoonski K and Allison JP: B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse. Immunity. 21:401–413. 2004. View Article : Google Scholar : PubMed/NCBI
37	Lenschow DJ, Walunas TL and Bluestone JA: CD28/B7 system of T cell costimulation. Annu Rev Immunol. 14:233–258. 1996. View Article : Google Scholar : PubMed/NCBI
38	Leplina OY, Tyrinova TV, Tikhonova MA, Ostanin AA and Chernykh ER: Interferon alpha induces generation of semi-mature dendritic cells with high pro-inflammatory and cytotoxic potential. Cytokine. 71:1–7. 2015. View Article : Google Scholar : PubMed/NCBI
39	van Lummel M, van Veelen PA, de Ru AH, Janssen GM, Pool J, Laban S, Joosten AM, Nikolic T, Drijfhout JW, Mearin ML, et al: Dendritic cells guide islet autoimmunity through a restricted and uniquely processed peptidome presented by high-risk HLA-DR. J Immunol. 196:3253–3263. 2016. View Article : Google Scholar : PubMed/NCBI
40	Foster GA, Xu L, Chidambaram AA, Soderberg SR, Armstrong EJ, Wu H and Simon SI: CD11c/CD18 signals very late antigen-4 activation to initiate foamy monocyte recruitment during the onset of hypercholesterolemia. J Immunol. 195:5380–5392. 2015. View Article : Google Scholar : PubMed/NCBI
41	Arnold IC, Mathisen S, Schulthess J, Danne C, Hegazy AN and Powrie F: CD11c(+) monocyte/macrophages promote chronic Helicobacter hepaticus-induced intestinal inflammation through the production of IL-23. Mucosal Immunol. 9:352–363. 2016. View Article : Google Scholar : PubMed/NCBI
42	Banchereau J, Pascual V and O'Garra A: From IL-2 to IL-37: The expanding spectrum of anti-inflammatory cytokines. Nat Immunol. 13:925–931. 2012. View Article : Google Scholar : PubMed/NCBI
43	Yoshimoto T, Takeda K, Tanaka T, Ohkusu K, Kashiwamura S, Okamura H, Akira S and Nakanishi K: IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: Synergism with IL-18 for IFN-gamma production. J Immunol. 161:3400–3407. 1998.PubMed/NCBI
44	Behzadi P, Behzadi E and Ranjbar R: IL-12 family cytokines: General characteristics, pathogenic microorganisms, receptors and signalling pathways. Acta Microbiol Immunol Hung. 63:1–25. 2016. View Article : Google Scholar : PubMed/NCBI
45	Vignali DA and Kuchroo VK: IL-12 family cytokines: Immunological playmakers. Nat Immunol. 13:722–728. 2012. View Article : Google Scholar : PubMed/NCBI
46	Belladonna ML, Renauld JC, Bianchi R, Vacca C, Fallarino F, Orabona C, Fioretti MC, Grohmann U and Puccetti P: IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cells. J Immunol. 168:5448–5454. 2002. View Article : Google Scholar : PubMed/NCBI
47	de Niet A, Stelma F, Jansen L, Sinnige MJ, Remmerswaal EB, Takkenberg RB, Kootstra NA, Reesink HW, van Lier RA and van Leeuwen EM: Restoration of T cell function in chronic hepatitis B patients upon treatment with interferon based combination therapy. J Hepatol. 64:539–546. 2016. View Article : Google Scholar : PubMed/NCBI
48	Aarntzen EH, De Vries IJ, Lesterhuis WJ, Schuurhuis D, Jacobs JF, Bol K, Schreibelt G, Mus R, De Wilt JH, Haanen JB, et al: Targeting CD4(+) T-helper cells improves the induction of antitumor responses in dendritic cell-based vaccination. Cancer Res. 73:19–29. 2013. View Article : Google Scholar : PubMed/NCBI