JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
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2025
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IF 11.2
Yue Li,Zhengrong Chen,Miaomiao Han,Zhen Duan,Ruizhe Li,Xinyi Cui,Haiyan Ge,Yilai Shu,Huabin Li,Rui He
Background Plasmacytoid dendritic cells (pDCs) are previously reported to induce immune tolerance to allergen by inhibiting allergic Th2 cell priming. However, there is limited knowledge on pDC function during Th2 effector phase of allergic asthma. Objective We aimed to investigate the role of pDCs in ongoing allergic asthma following airway sensitization and challenge with house mite dust (HDM). Methods BDCA2-DTR mice were used for pDC depletion. RNA-sequencing (RNA-seq) of sorted mouse lung pDCs, in vitro cell experiments, and in vivo CCR2 blockade or Tβ4 supplementation were performed to elucidate the underlying mechanism. Results: pDC depletion during HDM challenge enhanced CCR2-dependent inflammatory monocyte-derived cells (inf-MCs) accumulation, leading to exacerbated Th2-mediated allergic asthma phenotypes. RNA-seq analysis revealed an anti-inflammatory peptide thymosin β4 (Tβ4) among the most up-regulated genes in asthmatic lung pDCs. Airway epithelial cells-derived IL-33 was required for up-regulating Tβ4 expression in pDCs, which represented the main source of Tβ4 in asthmatic lungs. Importantly, Tβ4 supplementation reversed the exacerbation of asthmatic phenotypes in BDCA2-DTR mice. Alveolar macrophages were identified as the major source of CCL2 and the target of Tβ4 in asthmatic lungs. Mechanistically, Tβ4 inhibited IL-4/IL-13-induced phosphorylation of JAK1 and STAT6 and downstream EGR2 expression in macrophages, thereby reducing CCL2 expression and subsequent inf-MC recruitment. Unexpectedly, decreased serum Tβ4 levels were detected in mice and humans with ongoing allergic asthma. This could be due to increased uptake of Tβ4 by alveolar macrophage, which was required for its inhibitory effect on CCL2 expression. Conclusions Lung pDCs exert anti-inflammatory effects in allergic asthma via expressing Tβ4, which could have therapeutic potential.
研究领域:
免疫学
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呼吸病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2022
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IF 15.304
Xuan Li,Kun Xu,Ye He,Bailong Tao,Ke Li,Chuanchuan Lin,Jingwei Hu,Jing Wu,Yi Wu,Shaopeng Liu,Peng Liu,Huaiyu Wang,Kaiyong Cai
Ideal titanium implants are required to participate in bone repair actively to improve in situ osteointegration. However, the traditional surface functionalization methods of titanium implants are difficult to both achieve the active regulation and long-term stability of bioactive components. Here, a novel functionalized titanium which loaded with thymosin β4 (Tβ4) and covered by a hydrogel coating was designed and evaluated. A strong adhesion between the coating and the titanium substrate was realized by the synergistic action of borate ester bonds and surface topological structure. The hydrogel coating also achieved an in vivo adhesion between implant and tissue through hydrogen bonds and borate bonds. In addition, based on the ROS response property of borate bonds, the implant can release Tβ4 in response to the immune reaction of bone healing by regulating the polarization of macrophages, thereby reducing the fibrosis formation around the implant interface and promoting vascularization and osteointegration of bone defects.
研究领域:
生物材料
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组织工程
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免疫学
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骨科
✓ 已验证
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
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2023
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IF 4.6
Tianci Zhang,Zehong Xiang,Lei Liu,Zhifang Ma,Mikhail Panteleev,Fazly I. Ataullakhanov,Qiang Shi
Tight manipulation of the initial leukocytes infiltration and macrophages plasticity toward the M2 phenotype remain a challenge for diabetic wound healing. Inspired by the platelet function and platelet–macrophage interaction, a platelet-anchored polylactic acid- b -polyethylene glycol- b -polylactic acid (PLA-PEG-PLA) electrospun dressing is developed for inflammatory modulation and diabetic wounds healing acceleration. PLA-PEG-PLA electrospun meshes encapsulated with thymosin β 4 (T β 4) and CaCl 2 is fabricated with electrospinning, followed by immersion of electrospun mesh in platelet-rich plasma to firmly anchor the platelets. It is demonstrated that the anchored platelets on electrospun mesh can enhance the initial macrophage recruitment and control the T β 4 release from electrospun meshes to facilitate the macrophages polarization to the M2 phenotype. The inflammatory regulation promotes the expression of vascular endothelial growth factor and the migration of vascular endothelial cells for angiogenesis, resulting in accelerated diabetic wounds healing. Therefore, this work paved a new way to design platelet-inspired electrospun meshes for inflammation manipulation and diabetic wound healing.
研究领域:
生物医学工程
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组织工程
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伤口愈合
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炎症生物学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
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IF 26.8
Yutian Su,Fang Han,Huiming Chen,Yongming Li,Lan Sun,Lejin Liang,Longzhen Lu,Yilei Hui,Xiaotong Li,Baohong Sun,Zhengtu Li,Feng Ye,Youhui Lin
Biofilm-associated infections (BAIs) pose a serious threat to public health; in particular, a reactive oxygen species (ROS)-rich biofilm microenvironment can weaken the immunological response of antimicrobial natural killer (NK) cells. Conventional phototherapy cannot consistently inhibit the escape of planktonic bacteria from BAIs, thereby enabling persistent and recurrent infections. In this study, a thymosin β4 bio-orthogonally labeled NK (βNK) cytomembrane is proposed to decorate PtTe 2 nanozymes (βNK@PtTe 2 ) with hyperthermia and NK cells immune re-rousing to eliminate BAIs at all stages. Te-doped PtTe 2 exhibits outstanding ROS scavenging activity through an electron-enriched catalytic center with strong p-d orbital hybridization, and it generates a thermally driven force for disorganizing dense biofilm structures under laser irradiation. After biofilm elimination and ROS scavenging, the βNK cytomembrane in βNK@PtTe 2 selectively promotes chemotaxis and activates conventional NK (cNK) cells to kill planktonic bacteria that escape from biofilm disintegration at the infection site. In vivo, this therapeutic paradigm of immune microenvironment remodeling induces cNK cells to develop into long-lived tissue-resident NK (trNK) cells with an immunological memory against reinvading pathogens, thereby effectively preventing secondary infections. Overall, the as-prepared βNK@PtTe 2 combined with NK cells provides a systematic photo-immunologic strategy to inhibit recurrent biofilms and treat infectious diseases caused by such infections.
研究领域:
纳米医学
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免疫治疗
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光动力治疗
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感染性疾病
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生物膜生物学
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纳米酶催化
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免疫工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）