GENERATION OF TOLEROGENIC DENDRITIC CELLS UNDER THE PERSISTENT INFLAMMATION STIMULATION
Copyright © 2024 by the Shock Society..
ABSTRACT: Immunosuppression, commonly accompanied by persistent inflammation, is a key feature in the later phase of sepsis. However, the pathophysiological mechanisms underlying this phenomenon remain unclear. Dendritic cells (DCs), specifically tolerogenic DCs (tolDCs), play a crucial role in this process by regulating immune responses through inducing T cell anergy and releasing anti-inflammatory cytokines. Nevertheless, the existing cell models are inadequate for investigating tolDCs during the immunosuppressive phase of sepsis. Therefore, this study aimed to develop a novel in vitro model to generate tolDCs under chronic inflammatory conditions. We have successfully generated tolDCs by exposing them to sublethal lipopolysaccharide (LPS) for 72 h while preserving cell viability. Considering that IL-10-induced tolDCs (IL-10-tolDCs) are well-established models, we compared the immunological tolerance between LPS-tolDCs and IL-10-tolDCs. Our findings indicated that both LPS-tolDCs and IL-10-tolDCs exhibited reduced expression of maturation markers, whereas their levels of inhibitory markers were elevated. Furthermore, the immunoregulatory activities of LPS-tolDCs and IL-10-tolDCs were found to be comparable. These dysfunctions include impaired antigen presenting capacity and suppression of T cell activation, proliferation, and differentiation. Notably, compared with IL-10-tolDCs, LPS-tolDCs showed a reduced response in maturation and cytokine production upon stimulation, indicating their potential as a better model for research. Overall, in comparison with IL-10-tolDCs, our data suggest that the immunological dysfunctions shown in LPS-tolDCs could more effectively elucidate the increased susceptibility to secondary infections during sepsis. Consequently, LPS-tolDCs have emerged as promising therapeutic targets for ameliorating the immunosuppressed state in septic patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:61 |
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| Enthalten in: |
Shock (Augusta, Ga.) - 61(2024), 3 vom: 01. März, Seite 454-464 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Miao, Shumin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.04.2024 Date Revised 01.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1097/SHK.0000000000002318 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a ABSTRACT: Immunosuppression, commonly accompanied by persistent inflammation, is a key feature in the later phase of sepsis. However, the pathophysiological mechanisms underlying this phenomenon remain unclear. Dendritic cells (DCs), specifically tolerogenic DCs (tolDCs), play a crucial role in this process by regulating immune responses through inducing T cell anergy and releasing anti-inflammatory cytokines. Nevertheless, the existing cell models are inadequate for investigating tolDCs during the immunosuppressive phase of sepsis. Therefore, this study aimed to develop a novel in vitro model to generate tolDCs under chronic inflammatory conditions. We have successfully generated tolDCs by exposing them to sublethal lipopolysaccharide (LPS) for 72 h while preserving cell viability. Considering that IL-10-induced tolDCs (IL-10-tolDCs) are well-established models, we compared the immunological tolerance between LPS-tolDCs and IL-10-tolDCs. Our findings indicated that both LPS-tolDCs and IL-10-tolDCs exhibited reduced expression of maturation markers, whereas their levels of inhibitory markers were elevated. Furthermore, the immunoregulatory activities of LPS-tolDCs and IL-10-tolDCs were found to be comparable. These dysfunctions include impaired antigen presenting capacity and suppression of T cell activation, proliferation, and differentiation. Notably, compared with IL-10-tolDCs, LPS-tolDCs showed a reduced response in maturation and cytokine production upon stimulation, indicating their potential as a better model for research. Overall, in comparison with IL-10-tolDCs, our data suggest that the immunological dysfunctions shown in LPS-tolDCs could more effectively elucidate the increased susceptibility to secondary infections during sepsis. Consequently, LPS-tolDCs have emerged as promising therapeutic targets for ameliorating the immunosuppressed state in septic patients | ||
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| 700 | 1 | |a Gu, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Jinlong |e verfasserin |4 aut | |
| 700 | 1 | |a Pei, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yishan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zimeng |e verfasserin |4 aut | |
| 700 | 1 | |a Si, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Xiangdong |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jianfeng |e verfasserin |4 aut | |
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