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CD47 Potentiates Inflammatory Response in Systemic Lupus Erythematosus

Background: To investigate the role of CD47 in inflammatory responses in systemic lupus erythematosus (SLE). Methods: Expression of CD47 and signal regulatory protein alpha (SIRPα) by peripheral blood mononuclear cells (PBMCs) and changes in CD47 expression after exposure to SLE serum, healthy contr...

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Autores principales: Park, Jin Kyun, Lee, Ye Ji, Park, Ji Soo, Lee, Eun Bong, Song, Yeong Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151692/
https://www.ncbi.nlm.nih.gov/pubmed/34068752
http://dx.doi.org/10.3390/cells10051151
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author Park, Jin Kyun
Lee, Ye Ji
Park, Ji Soo
Lee, Eun Bong
Song, Yeong Wook
author_facet Park, Jin Kyun
Lee, Ye Ji
Park, Ji Soo
Lee, Eun Bong
Song, Yeong Wook
author_sort Park, Jin Kyun
collection PubMed
description Background: To investigate the role of CD47 in inflammatory responses in systemic lupus erythematosus (SLE). Methods: Expression of CD47 and signal regulatory protein alpha (SIRPα) by peripheral blood mononuclear cells (PBMCs) and changes in CD47 expression after exposure to SLE serum, healthy control (HC) serum, recombinant interferon (IFN)-α, or tumor necrosis factor (TNF)-α were examined. Human monocytes and THP1 cells were incubated with lipopolysaccharide (LPS), an anti-CD47 antibody, or both. TNF-α production was examined. Sera from SLE patients and HCs were screened to detect autoantibodies specific for CD47. Results: Twenty-five SLE patients and sixteen HCs were enrolled. CD47 expression by monocytes from SLE patients was higher than those from HCs (mean fluorescence intensity ± SD: 815.9 ± 269.4 vs. 511.5 ± 199.4, respectively; p < 0.001). CD47 expression by monocytes correlated with SLE disease activity (Spearman’s rho = 0.467, p = 0.019). IFN-α but not TNF-α, increased CD47 expression. Exposing monocytes to an anti-CD47 antibody plus LPS increased TNF-α production by 21.0 ± 10.9-fold (compared with 7.3 ± 5.5-fold for LPS alone). Finally, levels of autoantibodies against CD47 were higher in SLE patients than in HCs (21.4 ± 7.1 ng/mL vs. 16.1 ± 3.1 ng/mL, respectively; p = 0.02). Anti-CD47 antibody levels did not correlate with disease activity (Spearman’s rho = −0.11, p = 0.759) or CD47 expression on CD14 monocytes (Spearman’s rho = 0.079, p = 0.838) in patients. Conclusions: CD47 expression by monocytes is upregulated in SLE and correlates with disease activity. CD47 contributes to augmented inflammatory responses in SLE. Targeting CD47 might be a novel treatment for SLE.
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spelling pubmed-81516922021-05-27 CD47 Potentiates Inflammatory Response in Systemic Lupus Erythematosus Park, Jin Kyun Lee, Ye Ji Park, Ji Soo Lee, Eun Bong Song, Yeong Wook Cells Article Background: To investigate the role of CD47 in inflammatory responses in systemic lupus erythematosus (SLE). Methods: Expression of CD47 and signal regulatory protein alpha (SIRPα) by peripheral blood mononuclear cells (PBMCs) and changes in CD47 expression after exposure to SLE serum, healthy control (HC) serum, recombinant interferon (IFN)-α, or tumor necrosis factor (TNF)-α were examined. Human monocytes and THP1 cells were incubated with lipopolysaccharide (LPS), an anti-CD47 antibody, or both. TNF-α production was examined. Sera from SLE patients and HCs were screened to detect autoantibodies specific for CD47. Results: Twenty-five SLE patients and sixteen HCs were enrolled. CD47 expression by monocytes from SLE patients was higher than those from HCs (mean fluorescence intensity ± SD: 815.9 ± 269.4 vs. 511.5 ± 199.4, respectively; p < 0.001). CD47 expression by monocytes correlated with SLE disease activity (Spearman’s rho = 0.467, p = 0.019). IFN-α but not TNF-α, increased CD47 expression. Exposing monocytes to an anti-CD47 antibody plus LPS increased TNF-α production by 21.0 ± 10.9-fold (compared with 7.3 ± 5.5-fold for LPS alone). Finally, levels of autoantibodies against CD47 were higher in SLE patients than in HCs (21.4 ± 7.1 ng/mL vs. 16.1 ± 3.1 ng/mL, respectively; p = 0.02). Anti-CD47 antibody levels did not correlate with disease activity (Spearman’s rho = −0.11, p = 0.759) or CD47 expression on CD14 monocytes (Spearman’s rho = 0.079, p = 0.838) in patients. Conclusions: CD47 expression by monocytes is upregulated in SLE and correlates with disease activity. CD47 contributes to augmented inflammatory responses in SLE. Targeting CD47 might be a novel treatment for SLE. MDPI 2021-05-10 /pmc/articles/PMC8151692/ /pubmed/34068752 http://dx.doi.org/10.3390/cells10051151 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Park, Jin Kyun
Lee, Ye Ji
Park, Ji Soo
Lee, Eun Bong
Song, Yeong Wook
CD47 Potentiates Inflammatory Response in Systemic Lupus Erythematosus
title CD47 Potentiates Inflammatory Response in Systemic Lupus Erythematosus
title_full CD47 Potentiates Inflammatory Response in Systemic Lupus Erythematosus
title_fullStr CD47 Potentiates Inflammatory Response in Systemic Lupus Erythematosus
title_full_unstemmed CD47 Potentiates Inflammatory Response in Systemic Lupus Erythematosus
title_short CD47 Potentiates Inflammatory Response in Systemic Lupus Erythematosus
title_sort cd47 potentiates inflammatory response in systemic lupus erythematosus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151692/
https://www.ncbi.nlm.nih.gov/pubmed/34068752
http://dx.doi.org/10.3390/cells10051151
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