A vulnerability locus to multiple sclerosis maps to 7p15 in a region syntenic to an EAE locus in the rat

Coppin, Hélène; Mt, Ribouchon; Fontaine, Bertrand; Edan, Gilles; Clanet, M.; Mp, Roth

doi:10.1038/sj.gene.6364038

Cited by 8 publications

(4 citation statements)

References 25 publications

(27 reference statements)

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“…This data in combination with the protective role for NPY in EAE suggests that NPY may play a role in preventing the development of some autoimmune diseases via the regulation of T cell activation. Also, the potential relevance of NPY in MS has recently been emphasised in a genetic study revealing a susceptibility locus on human chromosome 7p15, a locus that encodes npy [94].…”

Section: Npy and Autoimmunitymentioning

confidence: 99%

NPY and Receptors in Immune and Inflammatory Diseases

Wheway

Herzog

Mackay

2007

CTMC

108

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Growing evidence suggests that neuropeptide Y (NPY) plays an important role in the immune system. NPY is produced by the central and peripheral nervous system but also by immune cells in response to activation. NPY has pleiotropic effects on both the innate and adaptive arms of the immune system, with effects ranging from the modulation of cell migration to macrophage, T helper (Th) cell cytokine release, and antibody production. Subsequent studies have confirmed the importance of this system in immunity in particular via the demonstration that Y1, a receptor for NPY, plays a fundamental role in autoimmunity and inflammation using Y1-deficient animals. Furthermore, clinical studies have suggested a role for NPY in other immune disorders such as asthma and arthritis. This review provides the latest information on the role of NPY and Y1 in the immune system, and discusses the potential new opportunities of this work for the development of a new generation of immuno-modulatory treatments of autoimmune and inflammatory diseases.

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Section: Npy and Autoimmunitymentioning

confidence: 99%

NPY and Receptors in Immune and Inflammatory Diseases

Wheway

Herzog

Mackay

2007

CTMC

108

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“…These observations confound the theory of a relationship between infections and antibodies in the pathogenesis of TS and related neuropsychiatric disorders. These days, the etiologies of many diseases, including diabetes and multiple sclerosis, point to an autoimmune mechanism [22][23][24][25]. Moreover, the results of previous studies indicate that both genetic and environmental factors play important roles [26].…”

Section: Introductionmentioning

confidence: 94%

Antineural antibody in patients with Tourette’s syndrome and their family members

Yeh

Wu²,

Tsung³

et al. 2005

J Biomed Sci

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SummaryIt has been proposed that antineural antibodies were present in patients with Tourette's syndrome (TS) and other neuropsychiatric disorders. The purpose of our study was to investigate the presence of antineural antibodies in the individuals with Tourette's syndrome and the family members of TS patients. The sera of four TS patients with no current streptococcal infection, their tic-free family members including father, mother and sibling, and a age-matched control group who were tic free were assayed for antineural antibodies directed against rat tissue and neurons in primary cell culture. There were prominent antineural antibodies present in TS patients and their first-degree family members, but not in the control group. Western blotting showed proteins of about 120 kDa in their sera that were not present in the sera of controls. The preliminary results of our study suggest the importance of genetic vulnerability in the immunological pathophysiology of tic disorders. Future studies should investigate the interactions of genetics, environment, infectious agents, and immunity on symptom expression in families with tic disorders.

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“…The published mouse cDNA sequences of the gene differ at the amino acid level, and several different nonsynonymous single nucleotide polymorphism in the protein-coding region are recorded in both mouse and human data sets (National Center for Biotechnology Information snp database). Susceptibilities to osteoporosis (61), multiple sclerosis (62), and asthma (63) have each been mapped by genome-wide linkage analysis to the vicinity of 7p15, the location of the human gpnmb gene. In conclusion, data described in this study suggest that GPNMB is a feedback regulator of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Gpnmb Is Induced in Macrophages by IFN-γ and Lipopolysaccharide and Acts as a Feedback Regulator of Proinflammatory Responses

Ripoll

Irvine

Ravasi

et al. 2007

The Journal of Immunology

189

187

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The process of inflammation requires the selective expression of a suite of genes in cells of the macrophage lineage. To identify candidate regulators of inflammation, we used cDNA microarrays to compare the transcriptome of inflammatory macrophages (thioglycolate-elicited peritoneal macrophages), bone marrow-derived macrophages, nonadherent spleen cells, and fibroblasts. We identified genes that were macrophage restricted and further elevated in inflammatory macrophages, and characterized the function of one such gene, gpnmb. Gpnmb mRNA expression was enriched in myelomonocytic cell lines and macrophage-related tissues and strongly up-regulated during macrophage differentiation. Epitope-tagged GPNMB expressed in RAW264.7 cells exhibited a perinuclear distribution and colocalized with the Golgi marker coat protein β. Upon activation of macrophages with IFN-γ and LPS, GPNMB translocated from the Golgi apparatus to vesicular compartments scattered toward the periphery. Gpnmb overexpression in RAW264.7 cells caused a 2-fold reduction in the production of the cytokines IL-6 and IL-12p40 and the inflammatory mediator NO in response to LPS. DBA mice, which have an inactivating point mutation in the gpnmb gene, exhibited reduced numbers of myeloid cells, elevated numbers of thioglycolate-elicited peritoneal macrophages, and higher levels of proinflammatory cytokines in response to LPS. Thus, GPNMB acts as a negative regulator of macrophage inflammatory responses.

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A vulnerability locus to multiple sclerosis maps to 7p15 in a region syntenic to an EAE locus in the rat

Cited by 8 publications

References 25 publications

NPY and Receptors in Immune and Inflammatory Diseases

NPY and Receptors in Immune and Inflammatory Diseases

Antineural antibody in patients with Tourette’s syndrome and their family members

Gpnmb Is Induced in Macrophages by IFN-γ and Lipopolysaccharide and Acts as a Feedback Regulator of Proinflammatory Responses

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