Toll-Like Receptors Mediate Opposing Dendritic Cell Effects on Treg/Th17 Balance in Mice With Intracerebral Hemorrhage-Reference-Cited by-同舟云学术

Toll-Like Receptors Mediate Opposing Dendritic Cell Effects on Treg/Th17 Balance in Mice With Intracerebral Hemorrhage

Published:2024-08 Issue:8 Volume:55 Page:2126-2138
ISSN:0039-2499
Container-title:Stroke
language:en
Short-container-title:Stroke

Author:

Zhu Li¹²^ORCID,Shang Junkui³^ORCID,Li Yinuo¹²^ORCID,Zhang Zhiying¹²,Fu Peiji¹²^ORCID,Zong Yan¹²^ORCID,Chen Shuai¹²^ORCID,Wang Junmin⁴,Zhang Jiewen³^ORCID,Wang Jian⁴^ORCID,Jiang Chao¹²³^ORCID

Affiliation:

1. Department of Neurology (L.Z., Y.L., Z.Z., P.F., Y.Z., S.C., C.J.), The Fifth Affiliated Hospital of Zhengzhou University, China.

2. The Laboratory of Cerebrovascular Diseases and Neuroimmunology (L.Z., Y.L., Z.Z., P.F., Y.Z., S.C., C.J.), The Fifth Affiliated Hospital of Zhengzhou University, China.

3. Department of Neurology, People’s Hospital of Zhengzhou University, China (J.S., J.Z., C.J.).

4. Department of Anatomy, School of Basic Medical Sciences, Zhengzhou University, China (Junmin Wang, Jian Wang).

Abstract

BACKGROUND: Dendritic cells (DCs) regulate the immune response associated with T lymphocytes, but their role in stroke remains unclear. In this study, we investigated the causal relationship between DCs and T-cell response in intracerebral hemorrhage (ICH) by focusing on TLRs (toll-like receptors) that may modulate the function of DCs. METHODS: We studied the effects of TLR4, TLR2, and TLR9 on DC-mediated T-cell response and the outcomes of ICH using male C57BL/6 and CD11c-DTx (diphtheria toxin) receptor mice. We administered specific agents intraperitoneally or orally and evaluated the results using flow cytometry, real-time polymerase chain reaction, Western blotting, immunofluorescence staining, histopathology, and behavioral tests. RESULTS: TLR4 and TLR2 activation induces DC maturation and reduces the ratio of regulatory T to T-helper 17 cells in the brain and periphery after ICH. When either of these receptors is activated, it can worsen neuroinflammation and exacerbate ICH outcomes. TLR9 also promotes DC maturation, stabilizing the number of DCs, particularly conventional DCs. TLR9 has the opposite effects on regulatory T/T-helper 17 balance, neuroinflammation, and ICH outcomes compared with TLR4 and TLR2. Upon stimulation, TLR4 and TLR9 may achieve these effects through the p38-MAPK (p38-mitogen-activated protein kinase)/MyD88 (myeloid differentiation primary response gene 88) and indoleamine 2,3-dioxygenase 1 (IDO1)/GCN2 (general control nonderepressible 2) signaling pathways, respectively. DCs act as intermediaries for TLR-mediated T-cell response. CONCLUSIONS: TLR-mediated opposing effects of DCs on T-cell response may provide novel strategies to treat ICH.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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