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  1. Article ; Online: Dietary Supplementation with 23-Hydroxy Ursolic Acid Reduces the Severity and Incidence of Acute Experimental Autoimmune Encephalomyelitis (EAE) in a Murine Model of Multiple Sclerosis.

    Asmis, Reto / Medrano, Megan T / Chase Huizar, Carol / Griffith, Wendell P / Forsthuber, Thomas G

    Nutrients

    2024  Volume 16, Issue 3

    Abstract: 23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation-resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and ...

    Abstract 23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation-resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Female C57BL/6 mice were fed either a defined low-calorie maintenance diet (MD) or an MD supplemented with 0.2% wgt/wgt 23-OH UA for 5 weeks prior to actively inducing EAE and during the 30 days post-immunization. We observed no difference in the onset of EAE between the groups of mice, but ataxia and EAE disease severity were suppressed by 52% and 48%, respectively, and disease incidence was reduced by over 49% in mice that received 23-OH UA in their diet. Furthermore, disease-associated weight loss was strikingly ameliorated in 23-OH UA-fed mice. ELISPOT analysis showed no significant differences in frequencies of T cells producing IL-17 or IFN-γ between 23-OH UA-fed mice and control mice, suggesting that 23-OH UA does not appear to regulate peripheral T cell responses. In summary, our findings in EAE mice strongly suggest that dietary 23-OH UA may represent an effective oral adjunct therapy for the prevention and treatment of relapsing-remitting MS.
    MeSH term(s) Female ; Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Multiple Sclerosis/drug therapy ; Ursolic Acid ; Disease Models, Animal ; Incidence ; Mice, Inbred C57BL ; Dietary Supplements
    Chemical Substances Ursolic Acid (P3M2575F3F)
    Language English
    Publishing date 2024-01-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu16030348
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Immunoregulation via Cell Density and Quorum Sensing-like Mechanisms: An Underexplored Emerging Field with Potential Translational Implications.

    Naoun, Adrian A / Raphael, Itay / Forsthuber, Thomas G

    Cells

    2022  Volume 11, Issue 15

    Abstract: Quorum sensing (QS) was historically described as a mechanism by which bacteria detect and optimize their population density via gene regulation based on dynamic environmental cues. Recently, it was proposed that QS or similar mechanisms may have broader ...

    Abstract Quorum sensing (QS) was historically described as a mechanism by which bacteria detect and optimize their population density via gene regulation based on dynamic environmental cues. Recently, it was proposed that QS or similar mechanisms may have broader applications across different species and cell types. Indeed, emerging evidence shows that the mammalian immune system can also elicit coordinated responses on a population level to regulate cell density and function, thus suggesting that QS-like mechanisms may also be a beneficial trait of the immune system. In this review, we explore and discuss potential QS-like mechanisms deployed by the immune system to coordinate cellular-level responses, such as T cell responses mediated via the common gamma chain (γc) receptor cytokines and the aryl hydrocarbon receptors (AhRs). We present evidence regarding a novel role of QS as a multifunctional mechanism coordinating CD4
    MeSH term(s) Animals ; Bacteria ; Cell Count ; Humans ; Immune System ; Mammals ; Quorum Sensing/genetics ; Signal Transduction
    Language English
    Publishing date 2022-08-06
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11152442
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Immunoregulation via Cell Density and Quorum Sensing-like Mechanisms

    Adrian A. Naoun / Itay Raphael / Thomas G. Forsthuber

    Cells, Vol 11, Iss 2442, p

    An Underexplored Emerging Field with Potential Translational Implications

    2022  Volume 2442

    Abstract: Quorum sensing (QS) was historically described as a mechanism by which bacteria detect and optimize their population density via gene regulation based on dynamic environmental cues. Recently, it was proposed that QS or similar mechanisms may have broader ...

    Abstract Quorum sensing (QS) was historically described as a mechanism by which bacteria detect and optimize their population density via gene regulation based on dynamic environmental cues. Recently, it was proposed that QS or similar mechanisms may have broader applications across different species and cell types. Indeed, emerging evidence shows that the mammalian immune system can also elicit coordinated responses on a population level to regulate cell density and function, thus suggesting that QS-like mechanisms may also be a beneficial trait of the immune system. In this review, we explore and discuss potential QS-like mechanisms deployed by the immune system to coordinate cellular-level responses, such as T cell responses mediated via the common gamma chain (γc) receptor cytokines and the aryl hydrocarbon receptors (AhRs). We present evidence regarding a novel role of QS as a multifunctional mechanism coordinating CD4 + and CD8 + T cell behavior during steady state and in response to infection, inflammatory diseases, and cancer. Successful clinical therapies such as adoptive cell transfer for cancer treatment may be re-evaluated to harness the effects of the QS mechanism(s) and enhance treatment responsiveness. Moreover, we discuss how signaling threshold perturbations through QS-like mediators may result in disturbances of the complex crosstalk between immune cell populations, undesired T cell responses, and induction of autoimmune pathology. Finally, we discuss the potential therapeutic role of modulating immune-system-related QS as a promising avenue to treat human diseases.
    Keywords quorum sensing ; immune system ; cytokines ; T cell homeostasis ; macrophage ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Ectopic Lymphoid Follicles in Multiple Sclerosis: Centers for Disease Control?

    Negron, Austin / Stüve, Olaf / Forsthuber, Thomas G

    Frontiers in neurology

    2020  Volume 11, Page(s) 607766

    Abstract: While the contribution of autoreactive ... ...

    Abstract While the contribution of autoreactive CD4
    Language English
    Publishing date 2020-12-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2020.607766
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Memory CD4

    Raphael, Itay / Joern, Rachel R / Forsthuber, Thomas G

    Cells

    2020  Volume 9, Issue 3

    Abstract: ... ...

    Abstract CD4
    MeSH term(s) Autoimmune Diseases/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cell Differentiation ; Humans ; Immunologic Memory/immunology
    Language English
    Publishing date 2020-02-25
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9030531
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Genomic, proteomic, and systems biology approaches in biomarker discovery for multiple sclerosis.

    Chase Huizar, Carol / Raphael, Itay / Forsthuber, Thomas G

    Cellular immunology

    2020  Volume 358, Page(s) 104219

    Abstract: Multiple sclerosis (MS) is a neuroinflammatory disorder characterized by autoimmune-mediated inflammatory lesions in CNS leading to myelin damage and axonal loss. MS is a heterogenous disease with variable and unpredictable disease course. Due to its ... ...

    Abstract Multiple sclerosis (MS) is a neuroinflammatory disorder characterized by autoimmune-mediated inflammatory lesions in CNS leading to myelin damage and axonal loss. MS is a heterogenous disease with variable and unpredictable disease course. Due to its complex nature, MS is difficult to diagnose and responses to specific treatments may vary between individuals. Therefore, there is an indisputable need for biomarkers for early diagnosis, prediction of disease exacerbations, monitoring the progression of disease, and for measuring responses to therapy. Genomic and proteomic studies have sought to understand the molecular basis of MS and find biomarker candidates. Advances in next-generation sequencing and mass-spectrometry techniques have yielded an unprecedented amount of genomic and proteomic data; yet, translation of the results into the clinic has been underwhelming. This has prompted the development of novel data science techniques for exploring these large datasets to identify biologically relevant relationships and ultimately point towards useful biomarkers. Herein we discuss optimization of omics study designs, advances in the generation of omics data, and systems biology approaches aimed at improving biomarker discovery and translation to the clinic for MS.
    MeSH term(s) Biomarkers/analysis ; Genomics/methods ; Humans ; Multiple Sclerosis/genetics ; Multiple Sclerosis/metabolism ; Proteomics/methods ; Systems Biology/methods
    Chemical Substances Biomarkers
    Language English
    Publishing date 2020-09-20
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80094-6
    ISSN 1090-2163 ; 0008-8749
    ISSN (online) 1090-2163
    ISSN 0008-8749
    DOI 10.1016/j.cellimm.2020.104219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Targeting "Retired Antigens" for Cancer Immunoprevention.

    Shoemaker, Robert H / Forsthuber, Thomas G

    Cancer prevention research (Philadelphia, Pa.)

    2017  Volume 10, Issue 11, Page(s) 607–608

    Abstract: Identification of immune targets for cancer immunoprevention, or immunotherapy, has historically focused on tumor-associated (self) antigens or neoantigens expressed on malignant cells. For self-antigens, overcoming tolerance can be a difficult challenge. ...

    Abstract Identification of immune targets for cancer immunoprevention, or immunotherapy, has historically focused on tumor-associated (self) antigens or neoantigens expressed on malignant cells. For self-antigens, overcoming tolerance can be a difficult challenge. Neoantigens do not suffer from this limitation, but the lack of recurrent mutations yielding common neoantigens that can be exploited in vaccines is a problem for many tumor types. Targeting "retired antigens," a specialized type of self-antigen, may have considerable advantages. Antigens no longer expressed in mature or aged individuals should pose reduced risk of autoimmune sequelae. Indeed, self-tolerance of these antigens may have naturally faded. Thus, when the retired antigens are highly expressed in cancer cells, it may be easier to overcome the remaining tolerance. Women who are BRCA1/2 carriers may be among the first to benefit as candidate retired antigens have been identified as highly expressed in ovarian and breast cancer cells. Although there is good preclinical data supporting this immune targeting concept, additional research is needed to understand the underlying immune phenomena and optimize the vaccine strategy.
    MeSH term(s) Aged ; Antigens, Neoplasm ; Cancer Vaccines ; Carcinoma, Ovarian Epithelial ; Female ; Humans ; Immunotherapy ; Neoplasms ; Receptors, Peptide ; Receptors, Transforming Growth Factor beta ; Vaccination
    Chemical Substances Antigens, Neoplasm ; Cancer Vaccines ; Receptors, Peptide ; Receptors, Transforming Growth Factor beta ; anti-Mullerian hormone receptor
    Language English
    Publishing date 2017-09-23
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2434717-6
    ISSN 1940-6215 ; 1940-6207
    ISSN (online) 1940-6215
    ISSN 1940-6207
    DOI 10.1158/1940-6207.CAPR-17-0188
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Targeting "bad" B cells in multiple sclerosis: Could laquinimod be part of the armamentarium?

    Forsthuber, Thomas G / Stuve, Olaf

    Neurology(R) neuroimmunology & neuroinflammation

    2016  Volume 3, Issue 5, Page(s) e283

    Language English
    Publishing date 2016-09-21
    Publishing country United States
    Document type Editorial
    ZDB-ID 2767740-0
    ISSN 2332-7812
    ISSN 2332-7812
    DOI 10.1212/NXI.0000000000000283
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: ELISPOT Techniques.

    Ji, Niannian / Forsthuber, Thomas G

    Methods in molecular biology (Clifton, N.J.)

    2016  Volume 1304, Page(s) 63–71

    Abstract: ... spots at the site of cytokine release by the cells under investigation (e.g., T cells) using pairs ... immune cells (e.g., peripheral blood mononuclear cells, PBMC), including suggestions for trouble-shooting and ...

    Abstract The enzyme-linked immunospot (ELISPOT) assay is a widely used method for enumerating antigen-specific cytokine-producing or antibody-secreting immune cells. It is one of the most effective immunological and diagnostic approaches to detect and quantify low-frequency cytokine- or antibody-producing cells in human and animal tissues, such as peripheral blood, lymph nodes, and spleen. Detection and quantification of specific cytokine-producing cells by the ELISPOT assay is based on the formation of visible spots at the site of cytokine release by the cells under investigation (e.g., T cells) using pairs of different capture and detection antibodies under optimized conditions.Here we focus mainly on practical, optimized protocols for cytokine ELISPOT assays for detection of mouse and human cytokine-producing immune cells (e.g., peripheral blood mononuclear cells, PBMC), including suggestions for trouble-shooting and optimizing steps for problematic tissue samples.
    MeSH term(s) Animals ; Cytokines ; Enzyme-Linked Immunospot Assay/methods ; Humans ; Mice
    Chemical Substances Cytokines
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/7651_2014_111
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Memory CD4 + T Cells in Immunity and Autoimmune Diseases

    Itay Raphael / Rachel R. Joern / Thomas G. Forsthuber

    Cells, Vol 9, Iss 3, p

    2020  Volume 531

    Abstract: CD4 + T helper (Th) cells play central roles in immunity in health and disease. While much is known about the effector function of Th cells in combating pathogens and promoting autoimmune diseases, the roles and biology of memory CD4 + Th cells are ... ...

    Abstract CD4 + T helper (Th) cells play central roles in immunity in health and disease. While much is known about the effector function of Th cells in combating pathogens and promoting autoimmune diseases, the roles and biology of memory CD4 + Th cells are complex and less well understood. In human autoimmune diseases such as multiple sclerosis (MS), there is a critical need to better understand the function and biology of memory T cells. In this review article we summarize current concepts in the field of CD4 + T cell memory, including natural history, developmental pathways, subsets, and functions. Furthermore, we discuss advancements in the field of the newly-described CD4 + tissue-resident memory T cells and of CD4 + memory T cells in autoimmune diseases, two major areas of important unresolved questions in need of answering to advance new vaccine design and development of novel treatments for CD4 + T cell-mediated autoimmune diseases.
    Keywords cd4 + t cells ; memory t cells ; autoimmune disease ; effector memory t cell ; central memory t cell ; tissue-resident t cell ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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