title: B cell-derived transforming growth factor-β1 expression limits the induction phase of autoimmune neuroinflammation.
abstract: Studies in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), have shown that regulatory B cells modulate the course of the disease via the production of suppressive cytokines. While data indicate a role for transforming growth factor (TGF)-β1 expression in regulatory B cell functions, this mechanism has not yet been tested in autoimmune neuroinflammation. Transgenic mice deficient for TGF-β1 expression in B cells (B-TGF-β1-/-) were tested in EAE induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG). In this model, B-TGF-β1-/-mice showed an earlier onset of neurologic impairment compared to their littermate controls. Exacerbated EAE susceptibility in B-TGF-β1-/-mice was associated with augmented CNS T helper (Th)1/17 responses. Moreover, selective B cell TGF-β1-deficiency increased the frequencies and activation of myeloid dendritic cells, potent professional antigen-presenting cells (APCs), suggesting that B cell-derived TGF-β1 can constrain Th1/17 responses through inhibition of APC activity. Collectively our data suggest that B cells can down-regulate the function of APCs, and in turn encephalitogenic Th1/17 responses, via TGF-β1, findings that may be relevant to B cell-targeted therapies.
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Kristbjörg
authors.initials: K
authors.lastname: Bjarnadóttir
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Mahdia
authors.initials: M
authors.lastname: Benkhoucha
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.|Division of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.affiliation: Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany.|Department of Neurology, University Medical Center, Georg August University, Göttingen, Germany.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Weber
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Payne
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Claude C A
authors.initials: CCA
authors.lastname: Bernard
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Molnarfi
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.|Department of Neurosciences, Division of Neurology, University Hospital of Geneva and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Patrice H
authors.initials: PH
authors.lastname: Lalive
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D017353:Gene Deletion; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000008:administration & dosage; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000276:immunology
chemical_list: D020381:Interleukin-17; C571327:Mog protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma