Blockade of D1-like dopaminergic receptors suppresses Th17-cell function in multiple sclerosis

2021 ◽  
Vol 121 (7) ◽  
pp. 82
Author(s):  
M.V. Melnikov ◽  
A.A. Sviridova ◽  
T.V. Solodova ◽  
A.V. Lopatina ◽  
M.V. Pashenkov ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Th17 Cell ◽  
Cell Function ◽  
Dopaminergic Receptors

scholarly journals Catecholamines as mediators of the neuroimmune interaction in multiple sclerosis

2019 ◽  
pp. 18-25
Author(s):  
М.В. Мельников ◽  
А.Н. Бойко ◽  
М.В. Пащенков ◽  
Е.И. Гусев
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Th17 Cell ◽  
Cell Function ◽  
Autoimmune Encephalomyelitis ◽  
Neuroimmune Interaction ◽  
Developing Directions ◽  
Modulating Functions ◽  
Experimental Autoimmune

Исследование нейроиммунных взаимодействий является одним из наиболее развивающихся направлений в изучении патогенеза рассеянного склероза. Механизмы этого взаимодействия до конца не ясны. Полагают, что ключевое значение в регуляции этого взаимодействия может принадлежать нейротрансмиттерам. Наибольшее внимание привлекают катехоламины, в частности, дофамин и норадреналин, рецепторы к которым экспрессируют клетки как нервной, так иммунной систем. Установлено, что модулируя функции иммунокомпетентных клеток дофамин и норадреналин способны влиять на течение как экспериментального аутоиммунного энцефаломиелита, так и рассеянного склероза. В работе представлен обзор литературы и собственных данных о значении дофамина и норадреналина в регуляции взаимодействия нервной и иммунной систем при рассеянном склерозе. Обсуждаются возможные механизмы, опосредующие влияние дофамина и норадреналина на патогенез рассеянного склероза, в частности, влияние дофамина и норадреналина на функционирование Th17-клеток, а также на опосредованный дендритными клетками Th17-зависимый иммунный ответ, играющий одну из ключевых патогенетических ролей при рассеянном склерозе. The neuroimmune interaction is one of fast developing directions in studying the pathogenesis of multiple sclerosis. The mechanism of this interaction is not sufficiently understood. The key role in regulation of this interaction is assumed to belong to neurotransmitters, among which catecholamines, specifically dopamine and norepinephrine, attract the greatest attention. Cells of both nervous and immune systems express dopaminergic and noradrenergic receptors. Dopamine and norepinephrine can influence the course of experimental autoimmune encephalomyelitis and multiple sclerosis by modulating functions of immune cells. This review presents literature and authors’ own data on the role of dopamine and norepinephrine in regulation of the nervous and immune system interaction in multiple sclerosis and focuses on possible mechanisms mediating the effect of dopamine and norepinephrine on the pathogenesis of multiple sclerosis, particularly the effect of dopamine and norepinephrine on the Th17 cell function and the dendritic cell-mediated Th17 immune response that plays a key role in the pathogenesis of multiple sclerosis.

scholarly journals SIRT1 deacetylates RORγt and enhances Th17 cell generation

2015 ◽  
Vol 212 (5) ◽  
pp. 607-617 ◽  
Author(s):  
Hyung W. Lim ◽  
Seung Goo Kang ◽  
Jae Kyu Ryu ◽  
Birgit Schilling ◽  
Mingjian Fei ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Cell Function ◽  
Cell Generation ◽  
Sirtuin 1 ◽  
T Helper 17 ◽  
Effector Cells ◽  
And Function

The balance of effector and regulatory T cell function, dependent on multiple signals and epigenetic regulators, is critical to immune self-tolerance. Dysregulation of T helper 17 (Th17) effector cells is associated with multiple autoimmune diseases, including multiple sclerosis. Here, we report that Sirtuin 1 (SIRT1), a protein deacetylase previously reported to have an antiinflammatory function, in fact promotes autoimmunity by deacetylating RORγt, the signature transcription factor of Th17 cells. SIRT1 increases RORγt transcriptional activity, enhancing Th17 cell generation and function. Both T cell–specific Sirt1 deletion and treatment with pharmacologic SIRT1 inhibitors suppress Th17 differentiation and are protective in a mouse model of multiple sclerosis. Moreover, analysis of infiltrating cell populations during disease induction in mixed hematopoietic chimeras shows a marked bias against Sirt1-deficient Th17 cells. These findings reveal an unexpected proinflammatory role of SIRT1 and, importantly, support the possible therapeutic use of SIRT1 inhibitors against autoimmunity.

The role of D2-like dopaminergic receptors in dopamine-mediated modulation of TH17-cells in multiple sclerosis

2021 ◽  
Vol 429 ◽  
pp. 118138
Author(s):  
Anna Lopatina ◽  
Tatiana Solodova ◽  
Anastasiya Sviridova ◽  
Mikhail Melnikov ◽  
Alexey Boyko
Keyword(s):  
Multiple Sclerosis ◽  
Th17 Cells ◽  
Dopaminergic Receptors

Anti-drug antibodies to antibody-based therapeutics in multiple sclerosis

2021 ◽  
pp. 1-9
Author(s):  
David Baker ◽  
A. Nazli Asardag ◽  
Olivia A. Quinn ◽  
Alex Efimov ◽  
Angray S. Kang
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
Remote Monitoring ◽  
Neutralizing Antibodies ◽  
Cell Function ◽  
Treatment Cessation ◽  
Human Antibodies ◽  
The Central Nervous System ◽  
Patient Responses ◽  
B Cell Subsets

Multiple sclerosis is the major demyelinating autoimmune disease of the central nervous system. Relapsing MS can be treated by a number of approved monoclonal antibodies that currently target: CD20, CD25 (withdrawn), CD49d and CD52. These all target potentially pathogenic memory B cell subsets and perhaps functionally inhibit pathogenic T cell function. These consist of chimeric, humanized and fully human antibodies. However, despite humanization it is evident that all of these monoclonal antibodies can induce binding and neutralizing antibodies ranging from < 1% to over 80% within a year of treatment. Importantly, it is evident that monitoring these allow prediction of future treatment-failure in some individuals and treatment cessation and switching therefore potentially limiting disease breakthrough and disability accumulation. In response to the COVID-19 pandemic and the need to avoid hospitals, shortened infusion times and extended dose intervals have been implemented, importantly, subcutaneous delivery of alternative treatments or formulations have been developed to allow for home treatment. Therefore, hospital-based and remote monitoring of ADA could therefore be advantageous to optimize patient responses in the future.

scholarly journals Potential Impact of B Cells on T Cell Function in Multiple Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Sara Ireland ◽  
Nancy Monson
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Function ◽  
The Central Nervous System ◽  
Potential Impact ◽  
Anti Cd20 ◽  
The Impact ◽  
Ms Pathogenesis

Multiple sclerosis is a chronic debilitating autoimmune disease of the central nervous system. The contribution of B cells in the pathoetiology of MS has recently been highlighted by the emergence of rituximab, an anti-CD20 monoclonal antibody that specifically depletes B cells, as a potent immunomodulatory therapy for the treatment of MS. However, a clearer understanding of the impact B cells have on the neuro-inflammatory component of MS pathogenesis is needed in order to develop novel therapeutics whose affects on B cells would be beneficial and not harmful. Since T cells are known mediators of the pathology of MS, the goal of this review is to summarize what is known about the interactions between B cells and T cells, and how current and emerging immunotherapies may impact B-T cell interactions in MS.

IFN-β limits Th17 cell lineage development: Implications in multiple sclerosis

Cytokine ◽  
2009 ◽  
Vol 48 (1-2) ◽  
pp. 70
Author(s):  
Leesa Pennell ◽  
Carole Galligan ◽  
Ramtin Rahbar ◽  
Beata Majchrzak ◽  
Thomas Murooka ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Th17 Cell ◽  
Cell Lineage
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