Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis

Wang, Na; Wu, Weiju; Cui, Qiang; Ma, Ning; Wu, Kunyi; Liú, Dan; Wang, Jia‐Xing; Yang, Xiao; Li, Xue; Diao, Teng-Yue; Liu, Jiayu; Li, Ang; Zhang, Baojun; Li, Zong‐Fang; Farrar, Conrad A.; Banda, Nirmal K.; Bayarri‐Olmos, Rafael; Garred, Peter; Zhou, Wuding; Li, Ké

doi:10.1002/art.41696

Cited by 11 publications

(9 citation statements)

References 32 publications

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“…VEC1 expressed high levels of protective genes, such as COLEC11 (antiautoimmune response), 16 PLA2G2A (antimicrobe), 17 and CTHRC1 (repair after VEC injury), 18 and it was thus annotated as protective VECs (Figure 3C; Figure S11B). VEC1 also highly expressed HLA (human leukocyte antigen) genes like HLA-DPA1, HLA-DRB1 , and HLA-DRA (Figure 3C), which might mediate antigen processing and presentation of exogenous peptide antigens via the major histocompatibility complex class (Figure 3D).…”

Section: Resultsmentioning

confidence: 99%

Cellular Landscapes of Nondiseased Human Cardiac Valves From End-Stage Heart Failure–Explanted Heart

Shu

Chen

et al. 2022

ATVB

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Background: Exploring the mechanisms of valvular heart disease at the cellular level may be useful to identify new therapeutic targets; however, the comprehensive cellular landscape of nondiseased human cardiac valve leaflets remains unclear. Methods: The cellular landscapes of nondiseased human cardiac valve leaflets (5 aortic valves, 5 pulmonary valves, 5 tricuspid valves, and 3 mitral valves) from end-stage heart failure patients undergoing heart transplantation were explored using single-cell RNA sequencing. Bioinformatics was used to identify the cell types, describe the cell functions, and investigate cellular developmental trajectories and interactions. Differences among the 4 types of cardiac valves at the cellular level were summarized. Pathological staining was performed to validate the key findings of single-cell RNA sequencing. An integrative analysis of our single-cell data and published genome-wide association study-based and bulk RNA sequencing-based data provided insights into the cell-specific contributions to calcific aortic valve diseases. Results: Six cell types were identified among 128 412 cells from nondiseased human cardiac valve leaflets. Valvular interstitial cells were the largest population, followed by myeloid cells, lymphocytes, valvular endothelial cells, mast cells, and myofibroblasts. The 4 types of cardiac valve had distinct cellular compositions. The intercellular communication analysis revealed that valvular interstitial cells were at the center of the communication network. The integrative analysis of our single-cell RNA sequencing data revealed key cellular subpopulations involved in the pathogenesis of calcific aortic valve diseases. Conclusions: The cellular landscape differed among the 4 types of nondiseased cardiac valve, which might explain their differences in susceptibility to pathological remodeling and valvular heart disease.

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Section: Resultsmentioning

confidence: 99%

Cellular Landscapes of Nondiseased Human Cardiac Valves From End-Stage Heart Failure–Explanted Heart

Shu

Chen

et al. 2022

ATVB

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“…In addition, another study reported that serum LRG1 levels were reduced after treatment with the anti-IL-6 receptor antibody tocilizumab [24]. T cells can differentiate into T helper 17 cells (Th17) or regulatory T cells (Tregs) under different stimulations [25]. The level of Th17 cells is positively associated with the disease activity of RA [26].…”

Section: Discussionmentioning

confidence: 99%

Serum proteomics analysis from rheumatoid arthritis patients receiving combination therapy of imrecoxib, total glucosides of paeony and two DMARDs

Hou

Fang

et al. 2022

Preprint

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Background：Rheumatoid arthritis (RA) is a chronic autoimmune disease. Imrecoxib, disease-modifying anti-rheumatic drugs (DMARDs) and total glucosides of paeony (TGPs) are common clinical therapies for RA. However, the exact mechanism of combination therapy for rheumatoid arthritis is still unclear. This study aims to explore the potential mechanism of this combination therapy for RA.Methods：Five RA patients who used this combination drug therapy were enrolled. Serum was collected at the first visit and the second visit after 3 months of continuous use of the combination treatment. Label-free quantitative proteomics was used to perform a comparative analysis of protein expression in serum after depletion of high-abundance proteins. The GO database was used to annotate the functions of differentially expressed proteins (DEPs).Results： A total of 257 reliable proteins were identified. Six proteins (IGKV3-20, TTR, LRG1, SERPINA3, F10 and NMNAT3) were downregulated, and one protein (HBD) was upregulated after three months of continuous combination drug treatment. Bioinformatics analysis showed that DEPs were primarily involved in various biological processes, such as metabolic processes, cellular processes and biological regulation. The identified DEPs have been reported to be involved in inflammation, cell proliferation, angiogenesis and oxidative stress. Therefore, these proteins have played important roles in RA progression.Conclusion： This combination drug therapy could alleviate the symptoms of RA by regulating these DEPs associated with RA in different ways. The DEPs identified may help to predict the treatment outcome of therapy for RA in the future.

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“…Unpaired t -test was employed for the comparison between two groups with unmatched data. Multiple comparison test, either One-way or Two-way, was used to compare the means of >2 independent groups [ 29 ]. p < 0.05 indicated a statistical significance level.…”

Section: Methodsmentioning

confidence: 99%

The Negative Impact of Triptolide on the Immune Function of Human Natural Killer Cells

Wang

Min

et al. 2023

Pharmaceuticals

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Triptolide (TP), a bioactive compound extracted the from traditional Chinese medicine Tripterygium wilfordii Hook F (TwHF), has been shown to be effective in treating several autoimmune diseases, and has suppressive effects in several key immune cells such as dendritic cells, T cells, and macrophages. However, it is unknown whether TP has an impact on natural killer (NK) cells. Here, we report that TP has suppressive effects on human NK cell activity and effector functions. The suppressive effects were observed in human peripheral blood mononuclear cell cultures and purified NK cells from healthy donors, as well as in purified NK cells from patients with rheumatoid arthritis. TP treatment induced downregulation of NK-activating receptor (CD54, CD69) expression and IFN-gamma secretion, in a dose-dependent manner. When exposed to K562 target cells, TP treatment induced inhibition of surface expression of CD107a and IFN-gamma synthesis in NK cells. Furthermore, TP treatment induced activation of inhibitory signaling (SHIP, JNK) and inhibition of MAPK signaling (p38). Thus, our findings demonstrate a previously unknown role for TP in NK cell functional suppression and reveal several key intracellular signaling that can be regulated by TP. Our findings also offer new insight into mechanisms of TP therapeutic treatment in autoimmune disease.

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Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis

Cited by 11 publications

References 32 publications

Cellular Landscapes of Nondiseased Human Cardiac Valves From End-Stage Heart Failure–Explanted Heart

Cellular Landscapes of Nondiseased Human Cardiac Valves From End-Stage Heart Failure–Explanted Heart

Serum proteomics analysis from rheumatoid arthritis patients receiving combination therapy of imrecoxib, total glucosides of paeony and two DMARDs

The Negative Impact of Triptolide on the Immune Function of Human Natural Killer Cells

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