Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and multiple organ damage. Toll-like receptor 7 (TLR7), an innate immune RNA sensor expressed in monocytes/macrophages, dendritic cells (DCs), and B cells, promotes disease progression. However, litt...

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Autores principales:	Yusuke Murakami, Ryutaro Fukui, Reika Tanaka, Yuji Motoi, Atsuo Kanno, Ryota Sato, Kiyoshi Yamaguchi, Hirofumi Amano, Yoichi Furukawa, Hitoshi Suzuki, Yusuke Suzuki, Naoto Tamura, Naomi Yamashita, Kensuke Miyake
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	toll-like receptor lupus nephritis inhibitory monoclonal antibody monocytes autoantibody Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/6ad713420c2a44b8aaac85ef2150dffd
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spelling	oai:doaj.org-article:6ad713420c2a44b8aaac85ef2150dffd2021-11-11T15:19:13ZAnti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes1664-322410.3389/fimmu.2021.777197https://doaj.org/article/6ad713420c2a44b8aaac85ef2150dffd2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.777197/fullhttps://doaj.org/toc/1664-3224Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and multiple organ damage. Toll-like receptor 7 (TLR7), an innate immune RNA sensor expressed in monocytes/macrophages, dendritic cells (DCs), and B cells, promotes disease progression. However, little is known about the cellular mechanisms through which TLR7 drives lupus nephritis. Here, we show that the anti-mouse TLR7 mAb, but not anti-TLR9 mAb, protected lupus-prone NZBWF1 mice from nephritis. The anti-TLR7 mAb reduced IgG deposition in glomeruli by inhibiting the production of autoantibodies to the RNA-associated antigens. We found a disease-associated increase in Ly6Clow patrolling monocytes that expressed high levels of TLR7 and had upregulated expression of lupus-associated IL-10, CD115, CD31, and TNFSF15 in NZBWF1 mice. Anti-TLR7 mAb abolished this lupus-associated increase in patrolling monocytes in the circulation, spleen, and glomeruli. These results suggested that TLR7 drives autoantibody production and lupus-associated monocytosis in NZBWF1 mice and, that anti-TLR7 mAb is a promising therapeutic tool targeting B cells and monocytes/macrophages.Yusuke MurakamiYusuke MurakamiRyutaro FukuiReika TanakaYuji MotoiAtsuo KannoRyota SatoKiyoshi YamaguchiHirofumi AmanoYoichi FurukawaHitoshi SuzukiYusuke SuzukiNaoto TamuraNaomi YamashitaKensuke MiyakeKensuke MiyakeFrontiers Media S.A.articletoll-like receptorlupus nephritisinhibitory monoclonal antibodymonocytesautoantibodyImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	toll-like receptor lupus nephritis inhibitory monoclonal antibody monocytes autoantibody Immunologic diseases. Allergy RC581-607
spellingShingle	toll-like receptor lupus nephritis inhibitory monoclonal antibody monocytes autoantibody Immunologic diseases. Allergy RC581-607 Yusuke Murakami Yusuke Murakami Ryutaro Fukui Reika Tanaka Yuji Motoi Atsuo Kanno Ryota Sato Kiyoshi Yamaguchi Hirofumi Amano Yoichi Furukawa Hitoshi Suzuki Yusuke Suzuki Naoto Tamura Naomi Yamashita Kensuke Miyake Kensuke Miyake Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes
description	Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and multiple organ damage. Toll-like receptor 7 (TLR7), an innate immune RNA sensor expressed in monocytes/macrophages, dendritic cells (DCs), and B cells, promotes disease progression. However, little is known about the cellular mechanisms through which TLR7 drives lupus nephritis. Here, we show that the anti-mouse TLR7 mAb, but not anti-TLR9 mAb, protected lupus-prone NZBWF1 mice from nephritis. The anti-TLR7 mAb reduced IgG deposition in glomeruli by inhibiting the production of autoantibodies to the RNA-associated antigens. We found a disease-associated increase in Ly6Clow patrolling monocytes that expressed high levels of TLR7 and had upregulated expression of lupus-associated IL-10, CD115, CD31, and TNFSF15 in NZBWF1 mice. Anti-TLR7 mAb abolished this lupus-associated increase in patrolling monocytes in the circulation, spleen, and glomeruli. These results suggested that TLR7 drives autoantibody production and lupus-associated monocytosis in NZBWF1 mice and, that anti-TLR7 mAb is a promising therapeutic tool targeting B cells and monocytes/macrophages.
format	article
author	Yusuke Murakami Yusuke Murakami Ryutaro Fukui Reika Tanaka Yuji Motoi Atsuo Kanno Ryota Sato Kiyoshi Yamaguchi Hirofumi Amano Yoichi Furukawa Hitoshi Suzuki Yusuke Suzuki Naoto Tamura Naomi Yamashita Kensuke Miyake Kensuke Miyake
author_facet	Yusuke Murakami Yusuke Murakami Ryutaro Fukui Reika Tanaka Yuji Motoi Atsuo Kanno Ryota Sato Kiyoshi Yamaguchi Hirofumi Amano Yoichi Furukawa Hitoshi Suzuki Yusuke Suzuki Naoto Tamura Naomi Yamashita Kensuke Miyake Kensuke Miyake
author_sort	Yusuke Murakami
title	Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes
title_short	Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes
title_full	Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes
title_fullStr	Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes
title_full_unstemmed	Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes
title_sort	anti-tlr7 antibody protects against lupus nephritis in nzbwf1 mice by targeting b cells and patrolling monocytes
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6ad713420c2a44b8aaac85ef2150dffd
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Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes

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