Predicted Disease-Specific Immune Infiltration Patterns Decode the Potential Mechanisms of Long Non-Coding RNAs in Primary Sjogren’s Syndrome

Cheng, Caiqi; Zhou, Jun; Chen, Ruiying; Shibata, Yo; Tanaka, Ryouichi; Wang, Jun; Zhang, Jiaming

doi:10.3389/fimmu.2021.624614

Cited by 10 publications

(14 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of cDC2s in the salivary glands of patients with pSS is clear12 13; however, the mechanisms that regulate the migration of cDC2s to the inflamed glands are unknown. Given the increased CX3CR1 expression in pSS cDC2s and since fractalkine levels (CX3CL1, the CX3CR1 ligand) are increased in the salivary gland of patients with pSS,33 the CX3CL1–CX3CR1 axis could mediate the presence of cDC2s in the inflamed glands of patients with pSS.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the important role of cDC2s to activate T and B cells, their contribution to pSS immunopathology has been poorly studied. Recently, transcriptomic analysis of minor salivary glands from patients with pSS confirmed the presence of a cDC2 gene signature in the inflamed salivary glands, which was strongly associated with CD4 + T cells 12 13. In patients with pSS, cDC2s are epigenetically altered with decreased miR-130a expression and increased expression of its target mitogen- and stress-activated protein kinase-1, important for proinflammatory cytokine production.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Deciphering the role of cDC2s in Sjögren’s syndrome: transcriptomic profile links altered antigen processes with IFN signature and autoimmunity

et al. 2022

View full text Add to dashboard Cite

ObjectiveType 2 conventional dendritic cells (cDC2s) are key orchestrators of inflammatory responses, linking innate and adaptative immunity. Here we explored the regulation of immunological pathways in cDC2s from patients with primary Sjögren’s syndrome (pSS).MethodsRNA sequencing of circulating cDC2s from patients with pSS, patients with non-Sjögren’s sicca and healthy controls (HCs) was exploited to establish transcriptional signatures. Phenotypical and functional validation was performed in independent cohorts.ResultsTranscriptome of cDC2s from patients with pSS revealed alterations in type I interferon (IFN), toll-like receptor (TLR), antigen processing and presentation pathways. Phenotypical validation showed increased CX3CR1 expression and decreased integrin beta-2 and plexin-B2 on pSS cDC2s. Functional validation confirmed impaired capacity of pSS cDC2s to degrade antigens and increased antigen uptake, including self-antigens derived from salivary gland epithelial cells. These changes in antigen uptake and degradation were linked to anti-SSA/Ro (SSA) autoantibodies and the presence of type I IFNs. In line with this, in vitro IFN-α priming enhanced the uptake of antigens by HC cDC2s, reflecting the pSS cDC2 profile. Finally, pSS cDC2s compared with HC cDC2s increased the proliferation and the expression of CXCR3 and CXCR5 on proliferating CD4+ T cells.ConclusionspSS cDC2s are transcriptionally altered, and the aberrant antigen uptake and processing, including (auto-)antigens, together with increased proliferation of tissue-homing CD4+ T cells, suggest altered antigen presentation by pSS cDC2s. These functional alterations were strongly linked to anti-SSA positivity and the presence of type I IFNs. Thus, we demonstrate novel molecular and functional pieces of evidence for the role of cDC2s in orchestrating immune response in pSS, which may yield novel avenues for treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Deciphering the role of cDC2s in Sjögren’s syndrome: transcriptomic profile links altered antigen processes with IFN signature and autoimmunity

et al. 2022

View full text Add to dashboard Cite

show abstract

“…To identify co-expressed candidate genes, the osteocyte transcriptome signature was analyzed by weighted gene co-expression network analysis (WGCNA) using the R package WGCNA (v1.69; R Foundation for Statistical Computing) 27 as previously described. 28 Independent dataset validation. The independent GEO dataset GSE30322 was employed to validate the significant genes.…”

Section: Methodsmentioning

confidence: 99%

Identification of mechanics-responsive osteocyte signature in osteoarthritis subchondral bone

Zhou

Cui

et al. 2022

Bone & Joint Research

Self Cite

View full text Add to dashboard Cite

Aims Osteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA. Methods Gene expression profiles of OA subchondral bone were used to identify disease-relevant genes and signalling pathways. RNA-sequencing data of a bone loading model were used to identify the loading-responsive gene set. Weighted gene co-expression network analysis (WGCNA) was employed to develop the osteocyte mechanics-responsive gene signature. Results A group of 77 persistent genes that are highly relevant to extracellular matrix (ECM) biology and bone remodelling signalling were identified in OA subchondral lesions. A loading responsive gene set, including 446 principal genes, was highly enriched in OA medial tibial plateaus compared to lateral tibial plateaus. Of this gene set, a total of 223 genes were identified as the main contributors that were strongly associated with osteocyte functions and signalling pathways, such as ECM modelling, axon guidance, Hippo, Wnt, and transforming growth factor beta (TGF-β) signalling pathways. We limited the loading-responsive genes obtained via the osteocyte transcriptome signature to identify a subgroup of genes that are highly relevant to osteocytes, as the mechanics-responsive osteocyte signature in OA. Based on WGCNA, we found that this signature was highly co-expressed and identified three clusters, including early, late, and persistently responsive genes. Conclusion In this study, we identified the mechanics-responsive osteocyte signature in OA-lesioned subchondral bone. Cite this article: Bone Joint Res 2022;11(6):362–370.

show abstract

“…Module-trait associations were calculated by module eigengenes. The module-trait associations revealed the relationships between OA and modules by calculating the correlation coefficient and one-way ANOVA ( Li et al, 2020 ; Cheng et al, 2021 ). Significant modules were identified according to the correlation coefficient and p -value.…”

Section: Methodsmentioning

confidence: 99%

Unbiased transcriptome mapping and modeling identify candidate genes and compounds of osteoarthritis

Cao

Zhang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage loss, subchondral bone remodeling, and synovial inflammation. Given that the current therapies for advanced OA patients are limited, the understanding of mechanisms and novel therapies are urgently needed. In this study, we employed the weighted gene co-expression network (WGCNA) method and the connectivity map (CMap) database to identify the candidate target genes and potential compounds. Four groups of co-expressing genes were identified as the OA-related modules. The biological annotations of these modules indicated some critical hallmarks of OA and aging, such as mitochondrial dysfunctions and abnormal energy metabolism, and the signaling pathways, such as MAPK, TNF, and PI3K/Akt signaling pathways. Some genes, such as RELA and GADD45B, were predicted to extensively involve these critical pathways, indicating their potential functions in OA mechanisms. Moreover, we constructed the co-expressing networks of modules and identified the hub genes based on network topology. GADD45B, MAFF, and MYC were identified and validated as the hub genes. Finally, anisomycin and MG-262 were predicted to target these OA-related modules, which may be the potential drugs for OA therapy. In conclusion, this study identified the significant modules, signaling pathways, and hub genes relevant to OA and highlighted the potential clinical value of anisomycin and MG-262 as novel therapies in OA management.

show abstract

Predicted Disease-Specific Immune Infiltration Patterns Decode the Potential Mechanisms of Long Non-Coding RNAs in Primary Sjogren’s Syndrome

Cited by 10 publications

References 35 publications

Deciphering the role of cDC2s in Sjögren’s syndrome: transcriptomic profile links altered antigen processes with IFN signature and autoimmunity

Deciphering the role of cDC2s in Sjögren’s syndrome: transcriptomic profile links altered antigen processes with IFN signature and autoimmunity

Identification of mechanics-responsive osteocyte signature in osteoarthritis subchondral bone

Unbiased transcriptome mapping and modeling identify candidate genes and compounds of osteoarthritis

Contact Info

Product

Resources

About