AGE-RELATED DECLINE IN VACCINATION EFFICACY: THE POTENTIAL ROLE OF MYELOID DERIVED SUPPRESSOR CELLS

2020 ◽  
pp. 785-795
Author(s):  
Ю. В. Перфильева ◽  
Б. В. Каральник ◽  
Е. О. Остапчук ◽  
А. Кали ◽  
Р. Т. Тлеулиева ◽  
...  
Keyword(s):  
Young People ◽  
Infectious Diseases ◽  
Older People ◽  
Suppressor Cells ◽  
Primary Response ◽  
Myeloid Derived Suppressor Cells ◽  
Age Related ◽  
Cellular And Humoral Immunity

Инфекционные заболевания у пожилых людей значительно более часты и смертность от них выше, чем у молодых людей. Вакцинация является наиболее эффективной и наименее затратной профилактической мерой при ряде инфекционных заболеваний. Однако вакцины, которые эффективны у молодых людей, часто неэффективны у пожилых людей старше 65 лет, причиной чего является постепенное снижение функциональных возможностей иммунной системы, происходящее с возрастом и называемое иммуностарением. Связанные с возрастом изменения в клеточном и гуморальном иммунитете ухудшают первичный ответ на вакцины и ослабляют развитие долговременной иммунной памяти. Исследования последних лет дают основание предполагать, что одной из возможных причин возникновения и поддержания иммуностарения в организме могут быть миелоидные супрессорные клетки ( Myeloid-Derived Suppressor Cells, MDSC ). Многочисленными исследованиями установлено, что MDSC способны ингибировать функции клеток врожденного и адаптивного иммунитета посредством ряда механизмов. В настоящем обзоре приводятся сведения, подчеркивающие роль MDSC в ингибировании иммунного ответа на вакцины при старении, а также обосновываются возможные пути преодоления данного иммунного препятствия. Infectious diseases in older people are much more frequent, and mortality from them is higher than in young people. Vaccination is the most effective and least expensive preventative measure for a number of infectious diseases. However, vaccines that are effective in young people are often ineffective in older people over 65, which is a result of a gradual decrease in the functional capacity of the immune systems, which occurs with age, and is called «immunosenescence». Age-related changes in the cellular and humoral immunity worsen the primary response to vaccines and weaken the development of long-term immunological memory. Recent studies suggest that one of the possible causes of the occurrence and maintenance of «immunosenescence» may be myeloid-derived suppressor cells ( MDSCs ). These cells have been shown to inhibit the functions of innate and adaptive immunity cells through a number of mechanisms. In this review, we provide information that emphasizes the role of MDSCs in inhibiting the immune response to vaccines during aging, and also substantiates possible ways to overcome this immunological obstacle.

The role of myeloid‐derived suppressor cells in chronic infectious diseases and the current methodology available for their study

2018 ◽  
Vol 105 (5) ◽  
pp. 857-872 ◽  
Author(s):  
Hernán F. Peñaloza ◽  
Diana Alvarez ◽  
Natalia Muñoz‐Durango ◽  
Bárbara M. Schultz ◽  
Pablo A. González ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells

scholarly journals Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

2021 ◽  
Author(s):  
Sujeong Yang ◽  
Sylvain Gigout ◽  
Angelo Molinaro ◽  
Yuko Naito-Matsui ◽  
Sam Hilton ◽  
...  
Keyword(s):  
Chondroitin Sulphate ◽  
Memory Loss ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Aged Mice ◽  
Age Related ◽  
Term Potentiation ◽  
Early Memory

AbstractPerineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.

501 VISTA regulates the differentiation and suppressive function of myeloid-derived suppressor cells

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A536-A536
Author(s):  
Juan Dong ◽  
Cassandra Gilmore ◽  
Hieu Ta ◽  
Keman Zhang ◽  
Sarah Stone ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Signaling Pathways ◽  
Immune Checkpoint ◽  
Suppressor Cells ◽  
Myeloid Cell ◽  
Myeloid Derived Suppressor Cells ◽  
Checkpoint Protein ◽  
Suppressive Function

BackgroundV-domain immunoglobulin suppressor of T cell activation (VISTA) is a B7 family inhibitory immune checkpoint protein and is highly expressed on myeloid cells and T cells.1 VISTA acts as both an inhibitory ligand when expressed on antigen-presenting cells and a receptor when expressed on T cells. Our recent study has shown that VISTA is a myeloid cell-specific immune checkpoint and that blocking VISTA can reprogram suppressive myeloid cells and promote a T cell-stimulatory tumor microenvironment.2 In this study, we further demonstrate that VISTA blockade directly alters the differentiation and the suppressive function of myeloid-derived suppressor cells (MDSC).MethodsFlow cytometry was performed to examine VISTA expression on MDSCs in multiple murine tumor models including the B16BL6 melanoma model, MC38 colon cancer model, and the KPC pancreatic cancer models. To examine the role of VISTA in controlling the differentiation and suppressive function of MDSCs, we cultured wild type (WT) and VISTA.KO bone marrow progenitor cells with GM-CSF and IL-6 to induce BM -derived MDSCs.ResultsOur preliminary results show that VISTA is highly expressed on M-MDSCs in B16BL6, MC38 and KPC tumors. In BM-derived MDSCs, VISTA deletion significantly altered the signaling pathways and the differentiation of MDSCs. Multiple inflammatory signaling pathways were downregulated in VISTA KO MDSCs, resulting in decreased production of cytokines such as IL1 and chemokines such as CCL2/4/9, as well as significantly impaired their ability to suppress the activation of CD8+ T cells. The loss of suppressive function in VISTA KO MDSCs is correlated with significantly reduced expression of iNOS. To validate the results from BM-MDSCs, we sorted CD11b+CD11c-Ly6C+Ly6G- M-MDSCs and CD11b+CD11c-Ly6G+ G-MDSCs from B16BL6 tumor tissues and tested the ability of a VISTA-blocking mAb to reverse the suppressive effects of tumor-derived MDSCs. Our results show that blocking VISTA impaired the suppressive function of tumor-derived M-MDSC but not G-MDSCs.ConclusionsTaken together, these results demonstrate a crucial role of VISTA in regulating the differentiation and function of MDSCs, and that blocking VISTA abolishes MDSC-mediated T cell suppression, thereby boosting.Ethics ApprovalAll in vivo studies were reviewed and approved by Institutional Animal Care and Use Committee (Approval number 2019-2142).ReferencesXu W, Hire T, Malarkannan, S. et al. The structure, expression, and multifaceted role of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation. Cell Mol Immunol 2018;15:438–446.Xu W, Dong J, Zheng Y, et al. Immune-checkpoint protein VISTA regulates antitumor immunity by controlling myeloid cell-mediated inflammation and immunosuppression. Cancer Immunol Res 2019;7:1497–510.

scholarly journals Immunomodulation by Inflammation during Liver and Gastrointestinal Tumorigenesis and Aging

2021 ◽  
Vol 22 (5) ◽  
pp. 2238
Author(s):  
Nao Nagai ◽  
Yotaro Kudo ◽  
Daisuke Aki ◽  
Hayato Nakagawa ◽  
Koji Taniguchi
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Antitumor Immunity ◽  
Suppressor Cells ◽  
Treg Cells ◽  
Cytotoxic T Cell ◽  
Myeloid Derived Suppressor Cells ◽  
Age Related ◽  
Immunosuppressive Tumor Microenvironment ◽  
Pro Inflammatory Cytokines

Chronic inflammation is thought to promote tumorigenesis and metastasis by several mechanisms, such as affecting tumor cells directly, establishing a tumor-supporting microenvironment, enhancing tumor angiogenesis, and suppressing antitumor immunity. In this review, we discuss the recent advances in our understanding of how inflammation induces the immunosuppressive tumor microenvironment, such as increasing the level of pro-inflammatory cytokines, chemokines, and immunosuppressive molecules, inducing immune checkpoint molecules and cytotoxic T-cell exhaustion, and accumulating regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs). The suppression of antitumor immunity by inflammation is especially examined in the liver and colorectal cancer. In addition, chronic inflammation is induced during aging and causes age-related diseases, including cancer, by affecting immunity. Therefore, we also discuss the age-related diseases regulated by inflammation, especially in the liver and colon.

scholarly journals The Role of Myeloid-Derived Suppressor Cells (MDSC) in Cancer Progression

Vaccines ◽  
2016 ◽  
Vol 4 (4) ◽  
pp. 36 ◽  
Author(s):  
Viktor Umansky ◽  
Carolin Blattner ◽  
Christoffer Gebhardt ◽  
Jochen Utikal
Keyword(s):  
Cancer Progression ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells

scholarly journals The Role of Education and Knowledge about Aging in Creating Young People’s Attitudes to the Elderly

2018 ◽  
Vol 8 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Jana Goriup ◽  
Danijela Lahe
Keyword(s):  
Young People ◽  
Older People ◽  
Negative Attitude ◽  
The Elderly ◽  
School Students ◽  
Negative Attitudes ◽  
Survey Results ◽  
People’S Attitudes ◽  
Intergenerational Cooperation

AbstractIntroduction: With the intensive growth in the number of older people and prolonged life span in the contemporary postmodern society, it has become increasingly important to build positive intergenerational cooperation and promote education on aging and older people, especially between younger and older generations. That is why the authors, on the basis of empirical research and scientific literature, examined knowledge about aging among young people and the connection between knowledge about aging and the formation of negative attitudes towards older people.Methods: The study involved 609 secondary school students aged 15 to 19 years.Results: The survey results showed that only one-fifth of the young population has good knowledge about aging. The relationship between knowledge about aging and ageism is negative, which means that young people with less knowledge about aging often have a negative attitude towards older people.Conclusions: Based on the obtained results, the authors underline the importance of integrating gerontology content in all stages of education.

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