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Toll-Like Receptors Mediate Opposing Dendritic Cell Effects on Treg/Th17 Balance in Mice With Intracerebral Hemorrhage.
Zhu, Li; Shang, Junkui; Li, Yinuo; Zhang, Zhiying; Fu, Peiji; Zong, Yan; Chen, Shuai; Wang, Junmin; Zhang, Jiewen; Wang, Jian; Jiang, Chao.
Afiliação
  • Zhu L; 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.
  • Shang J; 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.
  • Li Y; Department of Neurology, People's Hospital of Zhengzhou University, China (J.S., J.Z., C.J.).
  • Zhang Z; 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.
  • Fu P; 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.
  • Zong Y; 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.
  • Chen S; 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.
  • Wang J; 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.
  • Zhang J; 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.
  • Wang J; 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.
  • Jiang C; 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.
Stroke ; 55(8): 2126-2138, 2024 Aug.
Article em En | MEDLINE | ID: mdl-38920054
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Dendríticas / Hemorragia Cerebral / Linfócitos T Reguladores / Células Th17 / Camundongos Endogâmicos C57BL Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Dendríticas / Hemorragia Cerebral / Linfócitos T Reguladores / Células Th17 / Camundongos Endogâmicos C57BL Idioma: En Ano de publicação: 2024 Tipo de documento: Article