IgG Immune Complexes Break Immune Tolerance of Human Microglia

Marlijn van der Poel; Willianne Hoepel; Jörg Hamann; Inge Huitinga; Jeroen den Dunnen

doi:10.4049/jimmunol.2000130

IgG Immune Complexes Break Immune Tolerance of Human Microglia

Marlijn van der Poel, Willianne Hoepel, Jörg Hamann, Inge Huitinga, Jeroen den Dunnen

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Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

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Microglia are phagocytic cells involved in homeostasis of the brain and are key players in the pathogenesis of multiple sclerosis (MS). A hallmark of MS diagnosis is the presence of IgG Abs, which appear as oligoclonal bands in the cerebrospinal fluid. In this study, we demonstrate that myelin obtained post mortem from 8 out of 11 MS brain donors is bound by IgG Abs. Importantly, we show that IgG immune complexes strongly potentiate activation of primary human microglia by breaking their tolerance for microbial stimuli, such as LPS and Poly I:C, resulting in increased production of key proinflammatory cytokines, such as TNF and IL-1β. We identified FcγRI and FcγRIIa as the two main responsible IgG receptors for the breaking of immune tolerance of microglia. Combined, these data indicate that IgG immune complexes potentiate inflammation by human microglia, which may play an important role in MS-associated inflammation and the formation of demyelinating lesions.

Originele taal-2	Engels
Pagina's (van-tot)	2511-2518
Tijdschrift	Journal of Immunology
Volume	205
DOI's	https://doi.org/10.4049/jimmunol.2000130
Status	Gepubliceerd - 2020

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title = "IgG Immune Complexes Break Immune Tolerance of Human Microglia",

abstract = "Microglia are phagocytic cells involved in homeostasis of the brain and are key players in the pathogenesis of multiple sclerosis (MS). A hallmark of MS diagnosis is the presence of IgG Abs, which appear as oligoclonal bands in the cerebrospinal fluid. In this study, we demonstrate that myelin obtained post mortem from 8 out of 11 MS brain donors is bound by IgG Abs. Importantly, we show that IgG immune complexes strongly potentiate activation of primary human microglia by breaking their tolerance for microbial stimuli, such as LPS and Poly I:C, resulting in increased production of key proinflammatory cytokines, such as TNF and IL-1β. We identified FcγRI and FcγRIIa as the two main responsible IgG receptors for the breaking of immune tolerance of microglia. Combined, these data indicate that IgG immune complexes potentiate inflammation by human microglia, which may play an important role in MS-associated inflammation and the formation of demyelinating lesions.",

author = "{van der Poel}, Marlijn and Willianne Hoepel and J{\"o}rg Hamann and Inge Huitinga and Dunnen, {Jeroen den}",

note = "Copyright {\textcopyright} 2020 by The American Association of Immunologists, Inc.",

year = "2020",

doi = "10.4049/jimmunol.2000130",

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volume = "205",

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T1 - IgG Immune Complexes Break Immune Tolerance of Human Microglia

AU - van der Poel, Marlijn

AU - Hoepel, Willianne

AU - Hamann, Jörg

AU - Huitinga, Inge

AU - Dunnen, Jeroen den

PY - 2020

Y1 - 2020

N2 - Microglia are phagocytic cells involved in homeostasis of the brain and are key players in the pathogenesis of multiple sclerosis (MS). A hallmark of MS diagnosis is the presence of IgG Abs, which appear as oligoclonal bands in the cerebrospinal fluid. In this study, we demonstrate that myelin obtained post mortem from 8 out of 11 MS brain donors is bound by IgG Abs. Importantly, we show that IgG immune complexes strongly potentiate activation of primary human microglia by breaking their tolerance for microbial stimuli, such as LPS and Poly I:C, resulting in increased production of key proinflammatory cytokines, such as TNF and IL-1β. We identified FcγRI and FcγRIIa as the two main responsible IgG receptors for the breaking of immune tolerance of microglia. Combined, these data indicate that IgG immune complexes potentiate inflammation by human microglia, which may play an important role in MS-associated inflammation and the formation of demyelinating lesions.

AB - Microglia are phagocytic cells involved in homeostasis of the brain and are key players in the pathogenesis of multiple sclerosis (MS). A hallmark of MS diagnosis is the presence of IgG Abs, which appear as oligoclonal bands in the cerebrospinal fluid. In this study, we demonstrate that myelin obtained post mortem from 8 out of 11 MS brain donors is bound by IgG Abs. Importantly, we show that IgG immune complexes strongly potentiate activation of primary human microglia by breaking their tolerance for microbial stimuli, such as LPS and Poly I:C, resulting in increased production of key proinflammatory cytokines, such as TNF and IL-1β. We identified FcγRI and FcγRIIa as the two main responsible IgG receptors for the breaking of immune tolerance of microglia. Combined, these data indicate that IgG immune complexes potentiate inflammation by human microglia, which may play an important role in MS-associated inflammation and the formation of demyelinating lesions.

U2 - 10.4049/jimmunol.2000130

DO - 10.4049/jimmunol.2000130

M3 - Article

C2 - 32967931

SN - 0022-1767

VL - 205

SP - 2511

EP - 2518

JO - Journal of Immunology

JF - Journal of Immunology

ER -

IgG Immune Complexes Break Immune Tolerance of Human Microglia

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