Optimal strategies of the psoriasis treatment by suppressing the interactions between T-lymphocytes, keratinocytes and dendritic cells

2018 ◽  
Author(s):  
Evgenii Nikolaevich Khailov ◽  
Ellina Valer'evna Grigor'eva
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Optimal Strategies ◽  
Psoriasis Treatment

scholarly journals Optimal Strategies for Psoriasis Treatment

2018 ◽  
Vol 23 (3) ◽  
pp. 45 ◽  
Author(s):  
Ellina Grigorieva ◽  
Evgenii Khailov
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Optimal Strategies ◽  
Time Interval ◽  
Optimal Controls ◽  
Controlled System ◽  
Psoriasis Treatment ◽  
System A ◽  
Bounded Controls ◽  
The Pontryagin Maximum Principle

Within a given time interval we consider a nonlinear system of differential equations describing psoriasis treatment. Its phase variables define the concentrations of T-lymphocytes, keratinocytes and dendritic cells. Two scalar bounded controls are introduced into this system to reflect medication dosages aimed at suppressing interactions between T-lymphocytes and keratinocytes, and between T-lymphocytes and dendritic cells. For such a controlled system, a minimization problem of the concentration of keratinocytes at the terminal time is considered. For its analysis, the Pontryagin maximum principle is applied. As a result of this analysis, the properties of the optimal controls and their possible types are established. It is shown that each of these controls is either a bang-bang type on the entire time interval or (in addition to bang-bang type) contains a singular arc. The obtained analytical results are confirmed by numerical calculations using the software “BOCOP-2.0.5”. Their detailed analysis and the corresponding conclusions are presented.

scholarly journals FRI0015 PHENOTYPE AND FUNCTION OF THE PERIPHERAL BLOOD DENDRITIC CELLS OF PSORIASIS PATIENTS WITH AND WITHOUT ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 578.1-579
Author(s):  
S. Schnitte ◽  
A. Fuchs ◽  
T. Funk ◽  
A. C. Pecher ◽  
D. Dörfel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Flow Cytometry ◽  
Dendritic Cells ◽  
Psoriatic Arthritis ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Surface Proteins ◽  
Research Support ◽  
Cross Sectional ◽  
Cell Counts

Background:Psoriasis is a frequent skin disease that can appear with an arthritic manifestation in approximately 30% of the cases [1]. The underlying excessive immune reaction caused by pro-inflammatory cytokines can be triggered by several risk factors [2]. Various subgroups of Dendritic cells (DCs) in the skin play a crucial role in the induction of the dermal inflammatory response [3].Objectives:As the role of peripheral blood DCs remains unknown and the cause of an arthritic manifestation is still not completely understood [4], this project aimed to detect differences in phenotype or function of peripheral blood DCs in psoriatic patients with or without arthritis.Methods:We analyzed peripheral blood cells of 60 psoriasis patients with and without arthritis. Different DC subpopulations were detected by flow cytometry. Monocyte-derived DCs were cultured with or without Lipopolysaccharides to gain immature (iDC) and mature (mDC) cells. The DC phenotype was determined by staining with CD80, CD83, CD86, CD206, CCR7, CD1a, HLA-DR, CD40, GPN-MB, DC209 and CD14. Their T-cell stimulatory capability was analyzed by co-incubation with Carboxyfluorescein succinimidyl ester stained lymphocytes and the quantification of CD4+ T-lymphocytes afterwards. To measure the migration capacity DCs were seated into transwell chambers with a semipermeable membrane and partly supplemented with Macrophage Inflammatory Protein 3 Beta (Mip3b). Migrated cells were detected by flow cytometry. Measured cell counts were normalized to cell counts without Mip3b stimulation.Results:Comparing the factor of increase of migrated mDC counts due to mip3b stimulation, we detected a significant lower rate in samples of patients with arthritis (PsA) compared to those of patients without (Ps). Assays of mDCs without mip3b stimulation showed a significant higher count of migrated cells in the samples of the arthritic group [Figure 1]. Cell counts with Mip3b stimulation did vary slightly in the groups. The DC subpopulations and the expression of analyzed cell surface proteins did not show significant differences. The amounts of stimulated T-Lymphocytes did not differ significantly.Figure 1.Migration essay showing mDCs following Mip3b (+miß3b) as multiples of mDCs without stimulation (-mip3b). The factor of increase is significantly lower in patients with arthritis (PsA) compared to patients without (Ps). Absolute counts of migrated mDCs without Mip3b are significantly higher in the arthritic group. Cell counts with stimulation do not differ significantly (data not shown). N=24, p<0.05Conclusion:CCL19 (Mip3b) is a potent ligand to the CCR7 receptor inducing migration of DCs towards the lymphatic node [5]. The CCR7 amounts on the DC surface did not differ significantly in the groups. The mDCs without CCL19 stimulation migrated in higher amounts in samples of arthritic patients. Cell counts of stimulated DCs showed only slight differences. These results could be generated by a different appearance of the DCs of arthritic patients that might facilitate migration. Further experiments focusing on this aspect should be performed. A possible effect of disruptive factors (age, sex, medication…) needs to be clarified.References:[1]Henes, J.C., et al.,High prevalence of psoriatic arthritis in dermatological patients with psoriasis: a cross-sectional study.Rheumatol Int, 2014.34(2): p. 227-34.[2]Lee, E.B., et al.,Psoriasis risk factors and triggers.Cutis, 2018.102(5s): p. 18-20.[3]Kim, T.G., S.H. Kim, and M.G. Lee,The Origin of Skin Dendritic Cell Network and Its Role in Psoriasis.Int J Mol Sci, 2017.19(1).[4]Veale, D.J. and U. Fearon,The pathogenesis of psoriatic arthritis.Lancet, 2018.391(10136): p. 2273-2284.[5]Ricart, B.G., et al.,Dendritic cells distinguish individual chemokine signals through CCR7 and CXCR4.J Immunol, 2011.186(1): p. 53-61.Acknowledgments:This project was financially supported by Novartis Pharma GmbH.Disclosure of Interests:Sarah Schnitte Grant/research support from: Reaserch grant by Novartis, Alexander Fuchs: None declared, Tanja Funk: None declared, Ann-Christin Pecher: None declared, Daniela Dörfel: None declared, Jörg Henes Grant/research support from: Novartis, Roche-Chugai, Consultant of: Novartis, Roche, Celgene, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim,

Dendritic cells transduced with Rsf-1/HBXAP gene generate specific cytotoxic T lymphocytes against ovarian cancer in vitro

2010 ◽  
Vol 394 (3) ◽  
pp. 633-638 ◽  
Author(s):  
Li Sun ◽  
Beihua Kong ◽  
Xiugui Sheng ◽  
Jim Jinn-Chyuan Sheu ◽  
Ie-Ming Shih
Keyword(s):  
Ovarian Cancer ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes

Complementary Function of γδ T-Lymphocytes and Dendritic Cells in the Response to Isopentenyl-Pyrophosphate and Lipopolysaccharide Antigens

2005 ◽  
Vol 25 (3) ◽  
pp. 230-237 ◽  
Author(s):  
Angelo Martino ◽  
Rita Casetti ◽  
Alessandra D’Alessandri ◽  
Alessandra Sacchi ◽  
Fabrizio Poccia
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Isopentenyl Pyrophosphate ◽  
Complementary Function

A Bacterial Flagellin in Combination With Proinflammatory Cytokines Activates Human Monocyte-derived Dendritic Cells to Generate Cytotoxic T Lymphocytes Having Increased Homing Signals to Cancer

2014 ◽  
Vol 37 (1) ◽  
pp. 16-25 ◽  
Author(s):  
Cheol Yi Hong ◽  
Soo Young Kim ◽  
Hyun-Ju Lee ◽  
Shee Eun Lee ◽  
Sang Chul Lim ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Proinflammatory Cytokines ◽  
Human Monocyte

scholarly journals The Differential Anti-HIV Effect of a New Humic Substance-Derived Preparation in Diverse Cells of the Immune System

Acta Naturae ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 68-76
Author(s):  
G. V. Kornilaeva ◽  
A. E. Siniavin ◽  
A. Schultz ◽  
A. Germann ◽  
C. Moog ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Humic Substance ◽  
Immune Cells ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Infection Inhibition ◽  
Toxic Concentrations ◽  
Anti Hiv ◽  
Hiv 1

The anti-HIV activity of a new humic substance-derived preparation has been studied in individual pools of immune cells (CD4+ T lymphocytes, macrophages, dendritic cells). Near-complete inhibition of the HIV infection (by more than 90%) was achieved by treating each of the abovementioned cell types with non-toxic concentrations of the preparation. The inhibitory effect demonstrates the possibility of preventing the depletion of a significant portion of functionally important immune cells. A comparative study of infection inhibition in individual cell pools has allowed us to reveal the differences in the preparations effectiveness in each of the cell populations. A R5-tropic HIV-1 infection in macrophages exhibited maximum sensitivity to the preparation: 90% and 50% inhibition of the infection were observed in the presence of concentrations as low as 1.4 and 0.35 g/ml, respectively. A 15- and 19-fold higher concentration was required to achieve the same extent of inhibition in dendritic cells infected with the same strain. The effectiveness of the drug in CD4 + T lymphocytes is quite comparable to its effectiveness in macrophages. The drug is universally effective for both the T- and M-tropic variants of HIV-1.

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