cis interaction of CD153 with TCR/CD3 is crucial for the pathogenic activation of senescence-associated T cells
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved..
With age, senescence-associated (SA) CD4+ T cells that are refractory to T cell receptor (TCR) stimulation are increased along with spontaneous germinal center (Spt-GC) development prone to autoantibody production. We demonstrate that CD153 and its receptor CD30 are expressed in SA-T and Spt-GC B cells, respectively, and deficiency of either CD153 or CD30 results in the compromised increase of both cell types. CD153 engagement on SA-T cells upon TCR stimulation causes association of CD153 with the TCR/CD3 complex and restores TCR signaling, whereas CD30 engagement on GC B cells induces their expansion. Administration of an anti-CD153 antibody blocking the interaction with CD30 suppresses the increase in both SA-T and Spt-GC B cells with age and ameliorates lupus in lupus-prone mice. These results suggest that the molecular interaction of CD153 and CD30 plays a central role in the reciprocal activation of SA-T and Spt-GC B cells, leading to immunosenescent phenotypes and autoimmunity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Cell reports - 40(2022), 12 vom: 20. Sept., Seite 111373 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fukushima, Yuji [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.09.2022 Date Revised 19.10.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2022.111373 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM346469163 |
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| 100 | 1 | |a Fukushima, Yuji |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a cis interaction of CD153 with TCR/CD3 is crucial for the pathogenic activation of senescence-associated T cells |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a With age, senescence-associated (SA) CD4+ T cells that are refractory to T cell receptor (TCR) stimulation are increased along with spontaneous germinal center (Spt-GC) development prone to autoantibody production. We demonstrate that CD153 and its receptor CD30 are expressed in SA-T and Spt-GC B cells, respectively, and deficiency of either CD153 or CD30 results in the compromised increase of both cell types. CD153 engagement on SA-T cells upon TCR stimulation causes association of CD153 with the TCR/CD3 complex and restores TCR signaling, whereas CD30 engagement on GC B cells induces their expansion. Administration of an anti-CD153 antibody blocking the interaction with CD30 suppresses the increase in both SA-T and Spt-GC B cells with age and ameliorates lupus in lupus-prone mice. These results suggest that the molecular interaction of CD153 and CD30 plays a central role in the reciprocal activation of SA-T and Spt-GC B cells, leading to immunosenescent phenotypes and autoimmunity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a B cells | |
| 650 | 4 | |a CD153 | |
| 650 | 4 | |a CD30 | |
| 650 | 4 | |a CD4(+) T cells | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a T cell receptor | |
| 650 | 4 | |a aging | |
| 650 | 4 | |a autoimmune disease | |
| 650 | 4 | |a spontaneous germinal center | |
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| 700 | 1 | |a Sakamoto, Keiko |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuda, Michiyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshikai, Yasunobu |e verfasserin |4 aut | |
| 700 | 1 | |a Yagita, Hideo |e verfasserin |4 aut | |
| 700 | 1 | |a Kitamura, Daisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Chihara, Misaki |e verfasserin |4 aut | |
| 700 | 1 | |a Minato, Nagahiro |e verfasserin |4 aut | |
| 700 | 1 | |a Hattori, Masakazu |e verfasserin |4 aut | |
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