B cell-derived transforming growth factor-β1 expression limits the induction phase of autoimmune neuroinflammation

Kristbjörg Bjarnadóttir, Mahdia Benkhoucha, Doron Merkler, Martin S Weber, Natalie L. Payne, Claude C. A. Bernard, Nicolas Molnarfi, Patrice H Lalive

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number34594
Number of pages14
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 6 Oct 2016

Cite this

Bjarnadóttir, Kristbjörg ; Benkhoucha, Mahdia ; Merkler, Doron ; Weber, Martin S ; Payne, Natalie L. ; Bernard, Claude C. A. ; Molnarfi, Nicolas ; Lalive, Patrice H. / B cell-derived transforming growth factor-β1 expression limits the induction phase of autoimmune neuroinflammation. In: Scientific Reports. 2016 ; Vol. 6.
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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.",
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B cell-derived transforming growth factor-β1 expression limits the induction phase of autoimmune neuroinflammation. / Bjarnadóttir, Kristbjörg; Benkhoucha, Mahdia; Merkler, Doron; Weber, Martin S; Payne, Natalie L.; Bernard, Claude C. A.; Molnarfi, Nicolas; Lalive, Patrice H.

In: Scientific Reports, Vol. 6, 34594, 06.10.2016.

Research output: Contribution to journalArticleResearchpeer-review

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