Potent T cell mediated anti‐inflammatory role of the selective CB2 agonist lenabasum in multiple sclerosis

2021 ◽  
Author(s):  
Marta Tiberi ◽  
Tama Evron ◽  
Stefano Saracini ◽  
Laura Boffa ◽  
Nicola Biagio Mercuri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Anti Inflammatory ◽  
Cb2 Agonist

scholarly journals Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

2017 ◽  
Vol 31 (12) ◽  
pp. 5592-5608 ◽  
Author(s):  
Sabrina Giacoppo ◽  
Soundara Rajan Thangavelu ◽  
Francesca Diomede ◽  
Placido Bramanti ◽  
Pio Conti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Model ◽  
Periodontal Ligament ◽  
Periodontal Ligament Cell ◽  
Anti Inflammatory

scholarly journals GDP-l-fucose synthase is a CD4+ T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis

2018 ◽  
Vol 10 (462) ◽  
pp. eaat4301 ◽  
Author(s):  
Raquel Planas ◽  
Radleigh Santos ◽  
Paula Tomas-Ojer ◽  
Carolina Cruciani ◽  
Andreas Lutterotti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Cell Clone ◽  
Autoimmune Response ◽  
Guanosine Diphosphate ◽  
Immune Mediated ◽  
T Cell Clone ◽  
Positional Scanning ◽  
The Central Nervous System

Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system that develops in genetically susceptible individuals and likely requires environmental triggers. The autoantigens and molecular mimics triggering the autoimmune response in multiple sclerosis remain incompletely understood. By using a brain-infiltrating CD4+ T cell clone that is clonally expanded in multiple sclerosis brain lesions and a systematic approach for the identification of its target antigens, positional scanning peptide libraries in combination with biometrical analysis, we have identified guanosine diphosphate (GDP)–l-fucose synthase as an autoantigen that is recognized by cerebrospinal fluid–infiltrating CD4+ T cells from HLA-DRB3*–positive patients. Significant associations were found between reactivity to GDP-l-fucose synthase peptides and DRB3*02:02 expression, along with reactivity against an immunodominant myelin basic protein peptide. These results, coupled with the cross-recognition of homologous peptides from gut microbiota, suggest a possible role of this antigen as an inducer or driver of pathogenic autoimmune responses in multiple sclerosis.

scholarly journals Immune signatures of prodromal multiple sclerosis in monozygotic twins

2020 ◽  
Vol 117 (35) ◽  
pp. 21546-21556 ◽  
Author(s):  
Lisa Ann Gerdes ◽  
Claudia Janoschka ◽  
Maria Eveslage ◽  
Bianca Mannig ◽  
Timo Wirth ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
T Cell Subsets ◽  
Effector T Cell ◽  
Immune Signatures ◽  
Relapsing Remitting ◽  
Immune Traits

The tremendous heterogeneity of the human population presents a major obstacle in understanding how autoimmune diseases like multiple sclerosis (MS) contribute to variations in human peripheral immune signatures. To minimize heterogeneity, we made use of a unique cohort of 43 monozygotic twin pairs clinically discordant for MS and searched for disease-related peripheral immune signatures in a systems biology approach covering a broad range of adaptive and innate immune populations on the protein level. Despite disease discordance, the immune signatures of MS-affected and unaffected cotwins were remarkably similar. Twinship alone contributed 56% of the immune variation, whereas MS explained 1 to 2% of the immune variance. Notably, distinct traits in CD4+effector T cell subsets emerged when we focused on a subgroup of twins with signs of subclinical, prodromal MS in the clinically healthy cotwin. Some of these early-disease immune traits were confirmed in a second independent cohort of untreated early relapsing-remitting MS patients. Early involvement of effector T cell subsets thus points to a key role of T cells in MS disease initiation.

scholarly journals Role of IL-38 and Its Related Cytokines in Inflammation

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Xianli Yuan ◽  
Xiao Peng ◽  
Yan Li ◽  
Mingcai Li
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Receptor Antagonist ◽  
Inflammatory Responses ◽  
Structural Features ◽  
Specific Receptor ◽  
Anti Inflammatory ◽  
Near Future

Interleukin- (IL-) 38 is a recently discovered cytokine and is the tenth member of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor antagonist (IL-1Ra) and IL-36Ra. IL-36R is the specific receptor of IL-38, a partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by IL-36γ, thus inhibiting inflammatory responses. IL-38-related cytokines, including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and immune responses. The study of IL-38 and IL-38-related cytokines might provide new insights for developing anti-inflammatory treatments in the near future.

scholarly journals The Innate Immune Receptor CD14 Mediates Lymphocyte Migration in EAE

2015 ◽  
Vol 37 (1) ◽  
pp. 269-275 ◽  
Author(s):  
Ramona Halmer ◽  
Laura Davies ◽  
Yang Liu ◽  
Klaus Fassbender ◽  
Silke Walter
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Experimental Autoimmune Encephalomyelitis ◽  
T Cell Activation ◽  
Cell Activation ◽  
Innate Immune ◽  
Autoimmune Encephalomyelitis ◽  
Immune Receptors ◽  
Experimental Autoimmune

Background: Multiple sclerosis is the most common autoimmune disease of the central nervous system in young adults and histopathologically characterized by inflammation, demyelination and gliosis. It is considered as a CD4+ T cell-mediated disease, but also a disease-promoting role of the innate immune system has been proposed, based e.g. on the observation that innate immune receptors modulate disease severity of experimental autoimmune encephalomyelitis. Recent studies of our group provided first evidence for a key role of the innate immune LPS receptor (CD14) in pathophysiology of experimental autoimmune encephalomyelitis. CD14-deficient experimental autoimmune encephalomyelitis mice showed increased clinical symptoms and enhanced infiltration of monocytes and neutrophils in brain and spinal cord. Methods: In the current study, we further investigated the causes of the disease aggravation by CD14-deficiency and examined T cell activation, also focusing on the costimulatory molecules CTLA-4 and CD28, and T cell migration capacity over the blood brain barrier by FACS analysis, in vitro adhesion and transmigration assays. Results: In the results, we observed a significantly increased migration of CD14-deficient lymphocytes across an endothelial monolayer. In contrast, we did not see any differences in expression levels of TCR/CTLA-4 or TCR/CD28 and lymphocyte adhesion to endothelial cells from CD14-deficient compared to wildtype mice. Conclusion: The results demonstrate an important role of CD14 in migration of lymphocytes, and strengthen the importance of innate immune receptors in adaptive immune disorders, such as multiple sclerosis.

scholarly journals TGF-β Signaling in Cancer: Control by Negative Regulators and Crosstalk with Proinflammatory and Fibrogenic Pathways

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 384 ◽  
Author(s):  
Hendrik Ungefroren
Keyword(s):  
T Cell ◽  
Cell Biology ◽  
Transforming Growth Factor ◽  
T Cell Subsets ◽  
Negative Regulators ◽  
Inflammatory Signaling ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Anti Inflammatory

The transforming growth factor-β (TGF-β) family of secreted growth factors controls many aspects of cell and tissue physiology in multicellular eukaryotes. Dysregulation of its pathway contributes to a broad variety of pathologies, including fibrosis and cancer. TGF-β acts as a powerful tumor suppressor in epithelial cells but during later stages of tumor development cancer cells eventually respond to this cytokine with epithelial-mesenchymal transition (EMT), invasion, metastasis, and immunosuppression. This collection of articles covers some important aspects of TGF-β signaling in cancer. Two articles focus on the role of TGF-β in tumor immunity and pro- and anti-inflammatory signaling, with one analyzing its impact on T-cell biology and different T-cell subsets, while the other deals with modulation of anti-inflammatory signaling by TGF-β receptors through proinflammatory signaling by immune receptors and the role of mechanotransduction in TGF-β-dependent immunosuppression. Another set of four chapters highlights the fact that context-dependent responsiveness to TGF-β is largely controlled by inputs from negative regulators and cooperation with proinflammatory and proapoptotic pathways. This theme is extended to the regulation of Smad signaling by differential phosphorylation, eventually converting canonical Smad signaling to a mitogenic, fibrogenic and carcinogenic outcome. Last, it is discussed how another posttranslational modification, SUMOylation, can modify protein function and impact TGF-β-induced EMT, invasion and metastasis.

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