Antigen Presentation, Autoantigens, and Immune Regulation in Multiple Sclerosis and Other Autoimmune Diseases

Riedhammer, Christine; Weissert, Robert

doi:10.3389/fimmu.2015.00322

Cited by 95 publications

(82 citation statements)

References 350 publications

(371 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One of the important issues in MS and other inflammatory diseases of the CNS is understanding the requisites of autoantigenic peptides to induce CNS inflammation (Riedhammer and Weissert, 2015). Beside presentation of autoantigen-derived peptides on MHC molecules and the availability of reactive T-cell and B-cell repertoires as well as the presence of the target antigen in the CNS, pathways of cellular activation exist that allow disease development.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Identification of gene expression patterns critically involved in experimental autoimmune encephalomyelitis and multiple sclerosis

Herrmann

Barth

Greve

et al. 2016

Disease Models &Amp; Mechanisms

Self Cite

View full text Add to dashboard Cite

After encounter with a central nervous system (CNS)-derived autoantigen, lymphocytes leave the lymph nodes and enter the CNS. This event leads only rarely to subsequent tissue damage. Genes relevant to CNS pathology after cell infiltration are largely undefined. Myelin-oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), a chronic autoimmune disease of the CNS that results in disability. To assess genes that are involved in encephalitogenicity and subsequent tissue damage mediated by CNS-infiltrating cells, we performed a DNA microarray analysis from cells derived from lymph nodes and eluted from CNS in LEW.1AV1 (RT1av1) rats immunized with MOG 91-108. The data was compared to immunizations with adjuvant alone or naive rats and to immunizations with the immunogenic but not encephalitogenic MOG 73-90 peptide. Here, we show involvement of Cd38, Cxcr4 and Akt and confirm these findings by the use of Cd38-knockout (B6.129P2-Cd38tm1Lnd/J) mice, S1P-receptor modulation during EAE and quantitative expression analysis in individuals with MS. The hereby-defined underlying pathways indicate cellular activation and migration pathways mediated by G-protein-coupled receptors as crucial events in CNS tissue damage. These pathways can be further explored for novel therapeutic interventions.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Encephalitogenic peptides presented on MHC class II molecules to T cells lead to a program that forces lymphocytes to be activated and migrate towards the CNS (Riedhammer and Weissert, 2015). Adjuvant contributes by affecting multiple signaling pathways in lymphocytes as well as in organ-resident cells like in the CNS.…”

Section: Introductionmentioning

confidence: 99%

Identification of gene expression patterns critically involved in experimental autoimmune encephalomyelitis and multiple sclerosis

Herrmann

Barth

Greve

et al. 2016

Disease Models &Amp; Mechanisms

Self Cite

View full text Add to dashboard Cite

show abstract

“…In these disorders, immunologic tolerance to self-antigens is broken (1). This failure can be on the T cell as well as on the B cell side or on both sides.…”

Section: Introductionmentioning

confidence: 99%

“…In many autoimmune and paraneoplastic diseases of the CNS, the B cell response is much better characterized as compared with the T cell response (1, 9). T cell help is required for differentiation of B cells into plasma cells and affinity maturation of antibodies (10, 11).…”

Section: Introductionmentioning

confidence: 99%

Adaptive Immunity Is the Key to the Understanding of Autoimmune and Paraneoplastic Inflammatory Central Nervous System Disorders

Weissert

2017

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

There are common aspects and mechanisms between different types of autoimmune diseases such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), and autoimmune encephalitis (AE) as well as paraneoplastic inflammatory disorders of the central nervous system. To our present knowledge, depending on the disease, T and B cells as well as antibodies contribute to various aspects of the pathogenesis. Possibly the events leading to the breaking of tolerance between the different diseases are of great similarity and so far, only partially understood. Beside endogenous factors (genetics, genomics, epigenetics, malignancy) also exogenous factors (vitamin D, sun light exposure, smoking, gut microbiome, viral infections) contribute to susceptibility in such diseases. What differs between these disorders are the target molecules of the immune attack. For T cells, these target molecules are presented on major histocompatibility complex (MHC) molecules as MHC-bound ligands. B cells have an important role by amplifying the immune response of T cells by capturing antigen with their surface immunoglobulin and presenting it to T cells. Antibodies secreted by plasma cells that have differentiated from B cells are highly structure specific and can have important effector functions leading to functional impairment or/and lesion evolvement. In MS, the target molecules are mainly myelin- and neuron/axon-derived proteins; in NMOSD, mainly aquaporin-4 expressed on astrocytes; and in AE, various proteins that are expressed by neurons and axons.

show abstract

“…6,7 APCs of the myeloid lineage (m-APC), comprising DCs and macrophages (MΦ), and of the lymphoid lineage (B cells) are discerned. M-APCs, DCs in particular, have a key regulatory role in T cell tolerance and immunity against self-antigens.…”

Section: Regulation Of T Cell Autoimmunity By Myeloid Antigen Presentmentioning

confidence: 99%

Myelin oligodendrocyte glycoprotein has a dual role in T cell autoimmunity against central nervous system myelin

Hart

Weissert

2016

Multiple Sclerosis Journal - Experimental, Translational and Cl

Self Cite

View full text Add to dashboard Cite

BackgroundMyelin oligodendrocyte glycoprotein (MOG) is a candidate primary target of the autoimmune attack on the central nervous system (CNS) in multiple sclerosis (MS). However, the physiological function of MOG has been unclear for a long time.ObjectiveWe propose that MOG has a central role in the regulation of tolerance and autoimmunity.ConclusionThe interaction of MOG with DC-SIGN, an innate antigen receptor of myeloid antigen-presenting cells (m-APCs), present inside the CNS (microglia) or in draining lymph nodes (dendritic cells; DCs), keeps these cells in an immature/tolerogenic state. We postulate that this tolerogenic mechanism may be disturbed in MS by unknown factors.

show abstract

Antigen Presentation, Autoantigens, and Immune Regulation in Multiple Sclerosis and Other Autoimmune Diseases

Cited by 95 publications

References 350 publications

Identification of gene expression patterns critically involved in experimental autoimmune encephalomyelitis and multiple sclerosis

Identification of gene expression patterns critically involved in experimental autoimmune encephalomyelitis and multiple sclerosis

Adaptive Immunity Is the Key to the Understanding of Autoimmune and Paraneoplastic Inflammatory Central Nervous System Disorders

Myelin oligodendrocyte glycoprotein has a dual role in T cell autoimmunity against central nervous system myelin

Contact Info

Product

Resources

About