Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Maria C Jiménez-Martínez
 -- 783 2022-08-04 07:32:58 |
2 Number corrections in headers
Maria C Jiménez-Martínez
 Meta information modification 783 2022-08-04 09:52:17 | |
3 Introduction and results section were described with more detail.
Henry Velázquez-Soto
 + 309 word(s) 1092 2022-08-10 22:42:17 | |
4 format correct
Catherine Yang
 + 4 word(s) 1096 2022-08-11 03:10:17 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Velázquez-Soto, H.;  Jiménez-Martínez, M.C. B7 Molecules on Dendritic Cells after LPS Stimulation. Encyclopedia. Available online: https://encyclopedia.pub/entry/25836 (accessed on 31 December 2024).
Velázquez-Soto H,  Jiménez-Martínez MC. B7 Molecules on Dendritic Cells after LPS Stimulation. Encyclopedia. Available at: https://encyclopedia.pub/entry/25836. Accessed December 31, 2024.
Velázquez-Soto, Henry, Maria C Jiménez-Martínez. "B7 Molecules on Dendritic Cells after LPS Stimulation" Encyclopedia, https://encyclopedia.pub/entry/25836 (accessed December 31, 2024).
Velázquez-Soto, H., & Jiménez-Martínez, M.C. (2022, August 04). B7 Molecules on Dendritic Cells after LPS Stimulation. In Encyclopedia. https://encyclopedia.pub/entry/25836
Velázquez-Soto, Henry and Maria C Jiménez-Martínez. "B7 Molecules on Dendritic Cells after LPS Stimulation." Encyclopedia. Web. 04 August, 2022.
B7 Molecules on Dendritic Cells after LPS Stimulation
Edit

A key aspect of the inflammatory phenomenon is the involvement of costimulatory molecules expressed by antigen-presenting cells (APCs) and their ability to secrete cytokines to set instructions for adaptive immune response and to generate tolerance or inflammation. In a novel integrative approach, the evaluation of the kinetic expression of the membrane and soluble B7 costimulatory molecules CD86, ICOS-L, PDL1, PDL2 was presented, the transcription factor Interferon Regulatory Factor 4 (IRF4), and the cytokines produced by monocyte-derived dendritic cells (Mo-DCs) after challenging them with different concentrations of stimulation with E. coli lipopolysaccharide (LPS) for various lengths of time. The evaluation showed that the stimuli concentration and time of exposure to LPS are critical factors in modulating the dynamic expression pattern of membrane and soluble B7 molecules and cytokines.

B7 molecules Dendritic cells Cytokines IRF4 PDL1 PDL2 CD86 ICOSL LPS

1. Introduction

Whether an inflammatory response is evoked depends on different extrinsic and intrinsic characteristics of the antigen and the host, which together define immunogenicity [1]. One key aspect of the inflammatory response is the initiation of the adaptive immune response, which depends on the intertwined interaction between APCs and T cells[2]

Dendritic cells (DCs) are the primary antigen-presenting cells (APCs) due to their ability to sense, capture, process, and present antigens to T cells. The initiation and polarization of adaptative immune responses are well orchestrated by a display of signals, including the expression of membrane-bound costimulatory molecules, soluble costimulatory molecules, and the secretion of cytokines by DCs.[3][4] MHC/peptide–TCR interaction, costimulatory molecules’ ligation with receptors, and cytokine production are the main phenomenon occurring in the immunological synapse [5] .

The best known is the B7 costimulatory family, belonging to the immunoglobulin superfamily (IgSF).[6]  This family comprises costimulatory molecules that promote activation, polarization, and proliferation in T cells, such as CD86 and ICOS-L (inducible T cell costimulator ligand), and coinhibitory molecules that regulate the tolerance, suppression, and cellular death, such as PDL1 (programmed death ligand 1)  and PDL2 (programmed death ligand 2).[7] Interestingly, previous studies have proven that soluble forms of B7 molecules (sB7) can be detected in different tissues and supernatants of cell cultures.[8][9][10][11] This finding improves our understanding of the mechanism of action independently of cell contact interactions. However, it is still unclear whether a costimulatory or coinhibitory profile of sB7 molecules prevails under the steady or activation states of dendritic cells and what signals are conveyed to the T cells.

Critical regulators at the transcriptional level for B7 molecules expression have been reported. For example, CD80, CD86, and ICOS-L transcription factors include NF-kB and PU.1.[12][13][14] Recently, a novel transcription factor, the Interferon Regulatory Factor 4 (IRF4), was reported to be related to the expression of PDL1 and PDL2.[15][16][17]

B7 costimulatory molecules have received attention due to their relevance in clinical conditions such as allergies, autoimmunity, cancer, and transplantation.[18] Nevertheless, little is known about the behavior of these molecules in terms of both counterparts (stimulation and inhibition) in physiological conditions since most in vitro studies have evaluated only single molecules and single time points or have focused on samples of patients with specific clinical conditions. [19][20][21]

In addition to the expression of B7 molecules, autocrine-secreted cytokines play a relevant role in the expression of costimulatory molecules. Previous studies have suggested that IL-6 downregulates CD86- and HLA-associated molecules, impairing T-cell activation capacity in DCs;[22] meanwhile, TNF-α favors the expression of these molecules (in a viral context).[23] On the other hand, IFN-γ has been shown to directly regulate PDL1 and PDL2 expression in melanoma cells.[24] However, no studies have evaluated the profiles of cytokine and costimulatory molecules integrally.

This study aimed to explore the dynamics of B7 costimulatory molecules CD86,ICOSL, PDL1, and PDL2 in an integrative way, encompassing the membrane-bound costimulatory molecules, the soluble B7 costimulatory molecules, and the cytokines found in the microenvironment. The present model proposed Mo-DCs as archetype APCs due to their feasibility of obtaining a significant yield from peripheral blood mononuclear cells (PBMNCs), as reported in previous studies [25][26][27]. On the other hand, the use of LPS as a model antigen has been widely explored due to its capacity to activate innate immune cells and induce the expression of costimulatory molecules and cytokine secretion by DCs [28][29].

2. Results 

According to the findings, the researchers propose that B7 costimulatory molecules express differently in response to different antigen concentrations and stimulation times. Interestingly, the researchers observe an increased expression of the coinhibitory molecules PDL2 favored by IRF4 and PDL1 at an early stimulation time and under low antigen concentrations., and a second expression peak at 48h. The researchers also reaffirmed the proposed correlation between IRF4 and PDL2 expression [15][16]. Meanwhile, the costimulatory molecules CD86 and ICOS-L express at late times regardless of the antigen concentration. Similar to previous results, increased production of cytokines TNF-α, IL-6, and IL-10 can be observed at early times of stimulation, which may influence the PDL1 and PDL2 expression. In contrast, cytokines related to T-cell activation, IFN-γ, and IL-2, had a maximum secretion peak at the most prolonged time evaluated, similarly to the CD86 and ICOS-L expression. Although correlation analysis only showed an association between  IFN-γ and IL-2 with both CD86 and PDL1.

Concerning soluble forms of costimulatory molecules, the researchers found sPDL1 and sPDL2 to be the predominant soluble B7 forms in Mo-DC cultures over sCD86 in a 2:1 ratio, regardless of stimuli conditions in the culture. sICOSL was not detected in any of the conditions evaluated.

Figure 1. The behavior of B7 costimulatory molecules expression under LPS stimulation. Costimulatory molecules express in a differential fashion after LPS stimulation. Dendritic cells tend to increase PDL2 during the early stages of antigen exposition favored by IRF-4; ICOS-L expression is notable at 24 h. At 48 h, peak expression of molecules CD86 and PDL1 is observed. PDL2 and IRF-4 expression increase again at 48h. Regarding cytokines, TNF-α, IL-6, and IL-10 were found to increase at early stages; meanwhile, IFN-γ and IL-2 had a production peak at 48 h. Finally, soluble costimulatory molecules exhibited constant behavior regardless of the time of exposition or antigen concentration. sPDL1 and sPDL2 had twice the concentration of sCD86.

3. Conclusions

The data showed that Mo-DCs might be predisposed to respond silently and prone to initiating tolerogenic responses unless a threshold antigen concentration and stimulation time are reached, promoting B7 molecule activation and cytokine expression. The findings provide novel insights into dendritic cell function and allow a better understanding of its role in promoting or halting adaptative immune responses.  Additionally, the knowledge of transcription factors, cytokines, and costimulatory molecules also provides a framework for future research in various clinical settings and the design of treatment strategies.

The entry is from https://doi.org/10.3390/biom12070955

References

  1. Thomas Pradeu; Edgardo D. Carosella; On the definition of a criterion of immunogenicity. Proceedings of the National Academy of Sciences 2006, 103, 17858-17861, 10.1073/pnas.0608683103.
  2. Doreen Cantrell; Signaling in Lymphocyte Activation. Cold Spring Harbor Perspectives in Biology 2015, 7, a018788, 10.1101/cshperspect.a018788.
  3. Xiangyun Yin; Shuting Chen; Stephanie C. Eisenbarth; Dendritic Cell Regulation of T Helper Cells. Annual Review of Immunology 2021, 39, 759-790, 10.1146/annurev-immunol-101819-025146.
  4. Mar Cabeza-Cabrerizo; Ana Cardoso; Carlos M. Minutti; Mariana Pereira da Costa; Caetano Reis e Sousa; Dendritic Cells Revisited. Annual Review of Immunology 2021, 39, 131-166, 10.1146/annurev-immunol-061020-053707.
  5. Michael L. Dustin; The Immunological Synapse. Cancer Immunology Research 2014, 2, 1023-1033, 10.1158/2326-6066.cir-14-0161.
  6. Karl S. Peggs; James P. Allison; Co-stimulatory pathways in lymphocyte regulation: the immunoglobulin superfamily. British Journal of Haematology 2005, 130, 809-824, 10.1111/j.1365-2141.2005.05627.x.
  7. Mary Collins; Vincent Ling; Beatriz M Carreno; The B7 family of immune-regulatory ligands. Genome Biology 2004, 6, 223-223, 10.1186/gb-2005-6-6-223.
  8. Minyoung Her; D Kim; M Oh; H Jeong; I Choi; Increased expression of soluble inducible costimulator ligand (ICOSL) in patients with systemic lupus erythematosus. Lupus 2009, 18, 501-507, 10.1177/0961203308099176.
  9. Christopher Montemagno; Anais Hagege; Delphine Borchiellini; Brice Thamphya; Olivia Rastoin; Damien Ambrosetti; Juan Iovanna; Nathalie Rioux-Leclercq; Camillio Porta; Sylvie Negrier; et al.Jean-Marc FerreroEmmanuel ChamoreyGilles PagèsMaeva Dufies Soluble forms of PD-L1 and PD-1 as prognostic and predictive markers of sunitinib efficacy in patients with metastatic clear cell renal cell carcinoma. OncoImmunology 2019, 9, 1846901, 10.1080/2162402x.2020.1846901.
  10. Takemichi Fukasawa; Ayumi Yoshizaki; Satoshi Ebata; Kouki Nakamura; Ryosuke Saigusa; Shunsuke Miura; Takashi Yamashita; Megumi Hirabayashi; Yohei Ichimura; Takashi Taniguchi; et al.Yoshihide AsanoHisashi ShimizuYutaka KazoeKazuma MawatariTakehiko KitamoriShinichi Sato Contribution of Soluble Forms of Programmed Death 1 and Programmed Death Ligand 2 to Disease Severity and Progression in Systemic Sclerosis. Arthritis & Rheumatology 2017, 69, 1879-1890, 10.1002/art.40164.
  11. Pascale Jeannin; Giovanni Magistrelli; Jean-Pierre Aubry; Gersende Caron; Jean-François Gauchat; Toufic Renno; Nathalie Herbault; Liliane Goetsch; Aline Blaecke; Pierre-Yves Dietrich; et al.Jean-Yves BonnefoyYves Delneste Soluble CD86 Is a Costimulatory Molecule for Human T Lymphocytes. Immunity 2000, 13, 303-312, 10.1016/s1074-7613(00)00030-3.
  12. Deena M. Maurer; Juraj Adamik; Patricia M. Santos; Jian Shi; Michael R. Shurin; John M. Kirkwood; Walter J. Storkus; Lisa H. Butterfield; Dysregulated NF-κB–Dependent ICOSL Expression in Human Dendritic Cell Vaccines Impairs T-cell Responses in Patients with Melanoma. Cancer Immunology Research 2020, 8, 1554-1567, 10.1158/2326-6066.cir-20-0274.
  13. Shunsuke Kanada; Chiharu Nishiyama; Nobuhiro Nakano; Ryuyo Suzuki; Keiko Maeda; Mutsuko Hara; Nao Kitamura; Hideoki Ogawa; Ko Okumura; Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells. Blood 2011, 117, 2211-2222, 10.1182/blood-2010-06-291898.
  14. Gang-Ming Zou; Wen-Yang Hu; LIGHT regulates CD86 expression on dendritic cells through NF-κB, but not JNK/AP-1 signal transduction pathway. Journal of Cellular Physiology 2005, 205, 437-443, 10.1002/jcp.20420.
  15. Yan Gao; Simone A. Nish; Ruoyi Jiang; Lin Hou; Paula Licona-Limón; Jason S. Weinstein; Hongyu Zhao; Ruslan Medzhitov; Control of T Helper 2 Responses by Transcription Factor IRF4-Dependent Dendritic Cells. Immunity 2013, 39, 722-732, 10.1016/j.immuni.2013.08.028.
  16. Bryan Vander Lugt; Jeremy Riddell; Aly A. Khan; Jason A. Hackney; Justin Lesch; Jason Devoss; Matthew T. Weirauch; Harinder Singh; Ira Mellman; Transcriptional determinants of tolerogenic and immunogenic states during dendritic cell maturation. Journal of Cell Biology 2017, 216, 779-792, 10.1083/jcb.201512012.
  17. Jing-Ping Zhang; Zhihui Song; Hong-Bo Wang; Lang Lang; Yuan-Zhong Yang; Wenming Xiao; Daniel E. Webster; Wei Wei; Stefan K. Barta; Marshall E. Kadin; et al.Louis M. StaudtMasao NakagawaYibin Yang A novel model of controlling PD-L1 expression in ALK+ anaplastic large cell lymphoma revealed by CRISPR screening. Blood 2019, 134, 171-185, 10.1182/blood.2019001043.
  18. Henry Velazquez-Soto; Fernanda Real; Maria C Jiménez-Martínez; Historical evolution, overview, and therapeutic manipulation of co-stimulatory molecules. World Journal of Immunology 2022, 12, 1-8, 10.5411/wji.v12.i1.1.
  19. Alexandra Aicher; Martha Hayden-Ledbetter; William A. Brady; Antonio Pezzutto; Guenther Richter; Dario Magaletti; Sonya Buckwalter; Jeffrey A. Ledbetter; Edward A. Clark; Characterization of Human Inducible Costimulator Ligand Expression and Function. The Journal of Immunology 2000, 164, 4689-4696, 10.4049/jimmunol.164.9.4689.
  20. Janine Obendorf; Pablo Renner Viveros; Michael Fehlings; Christian Klotz; Toni Aebischer; Ralf Ignatius; Increased expression of CD25, CD83, and CD86, and secretion of IL-12, IL-23, and IL-10 by human dendritic cells incubated in the presence of Toll-like receptor 2 ligands and Giardia duodenalis. Parasites & Vectors 2013, 6, 317-317, 10.1186/1756-3305-6-317.
  21. Marta Rodríguez-García; Filippos Porichis; Olivier G. De Jong; Karen Levi; Thomas J. Diefenbach; Jeffrey D. Lifson; Gordon J. Freeman; Bruce D. Walker; Daniel E. Kaufmann; Daniel G. Kavanagh; et al. Expression of PD-L1 and PD-L2 on human macrophages is up-regulated by HIV-1 and differentially modulated by IL-10. Journal of Leukocyte Biology 2010, 89, 507-515, 10.1189/jlb.0610327.
  22. Yosuke Ohno; Hidemitsu Kitamura; Norihiko Takahashi; Junya Ohtake; Shun Kaneumi; Kentaro Sumida; Shigenori Homma; Hideki Kawamura; Nozomi Minagawa; Susumu Shibasaki; et al.Akinobu Taketomi IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen-specific CD4+ T cells. Cancer Immunology, Immunotherapy 2016, 65, 193-204, 10.1007/s00262-015-1791-4.
  23. Jose M. Trevejo; Michael W. Marino; Nicola Philpott; Regis Josien; Elizabeth C. Richards; Keith B. Elkon; Erik Falck-Pedersen; TNF-α-dependent maturation of local dendritic cells is critical for activating the adaptive immune response to virus infection. Proceedings of the National Academy of Sciences 2001, 98, 12162-12167, 10.1073/pnas.211423598.
  24. Angel Garcia-Diaz; Daniel Sanghoon Shin; Blanca Homet Moreno; Justin Saco; Helena Escuin-Ordinas; Gabriel Abril Rodriguez; Jesse M. Zaretsky; Lu Sun; Willy Hugo; Xiaoyan Wang; et al.Giulia ParisiCristina Puig SausDavis Y. TorrejonThomas G. GraeberBegonya Comin-AnduixSiwen Hu-LieskovanRobert DamoiseauxRoger S. LoAntoni Ribas Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression. Cell Reports 2017, 19, 1189-1201, 10.1016/j.celrep.2017.04.031.
  25. F Sallusto; A Lanzavecchia; Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.. Journal of Experimental Medicine 1994, 179, 1109-1118, 10.1084/jem.179.4.1109.
  26. Yuko Osugi; Slavica Vuckovic; Derek N. J. Hart; Myeloid blood CD11c+ dendritic cells and monocyte-derived dendritic cells differ in their ability to stimulate T lymphocytes. Blood 2002, 100, 2858-2866, 10.1182/blood.v100.8.2858.
  27. Paula Sato; Telma Oshiro; Érika Passos; Tatiana Miranda; Constância Diogo; Claudia Fonseca; Aya Sadahiro; Sandro de Almeida; Maria Shikanai-Yasuda; Monocyte-Derived Dendritic Cells Can Revert In Vitro Antigen-Specific Cellular Anergy in Active Human Paracoccidioidomycosis. Journal of Fungi 2021, 7, 201, 10.3390/jof7030201.
  28. Kaveh Abdi; Nevil J. Singh; Polly Matzinger; Lipopolysaccharide-Activated Dendritic Cells: “Exhausted” or Alert and Waiting?. The Journal of Immunology 2012, 188, 5981-5989, 10.4049/jimmunol.1102868.
  29. Garth L. J. Dixon; Phillippa J. Newton; Benjamin M. Chain; David Katz; Svein Rune Andersen; Simon Wong; Peter van der Ley; Nigel Klein; Robin E. Callard; Dendritic Cell Activation and Cytokine Production Induced by Group B Neisseria meningitidis : Interleukin-12 Production Depends on Lipopolysaccharide Expression in Intact Bacteria. Infection and Immunity 2001, 69, 4351-4357, 10.1128/iai.69.7.4351-4357.2001.
More
©Text is available under the terms and conditions of the Creative Commons-Attribution ShareAlike (CC BY-SA) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Immunology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Henry Velázquez-Soto
,
Maria C Jiménez-Martínez
View Times: 735
Revisions: 4 times (View History)
Update Date: 11 Aug 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback