The landscape of T and B lymphocytes interaction and synergistic effects of Th1 and Th2 type response in the involved tissue of IgG4-RD revealed by single cell transcriptome analysis

Cai, Shaozhe; Chen, Yu; Hu, Ziwei; Zhou, Tianshu; Huang, Yanli; Lin, Sheng‐Yan; Gao, Rongfen; Zhong, Jixin; Dong, Lingli

doi:10.1016/j.jaut.2022.102944

Cited by 13 publications

(20 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To our knowledge, the present study is the first to comprehensively depict the single-cell transcriptional landscapes of SMGs in IgG4-RD. The results of our study are in accordance with the results of two previous studies that described immune cell heterogeneity in PB and B/T cell heterogeneity in SMGs 4 9. The results of B cells and plasma cells showed that ectopic GC reactions appeared in the SMGs of IgG4-RD, which is consistent with the findings of Cai et al 4.…”

Section: Discussionsupporting

confidence: 93%

“…B cells, T cells, especially T follicular helper (Tfh) cells, CD4 + cytotoxic T lymphocytes (CTLs) and macrophages participate in the inflammation and fibrosis process in the disease 2. Ectopic germinal centres (GCs) can be found in IgG4-RD-affected tissues such as the lacrimal gland, salivary gland and pancreas 3 4. Tfh cells provide essential help for B cell affinity maturation, class switch recombination and plasma and memory B cell generation within the GC 5.…”

Section: Introductionmentioning

confidence: 99%

“…It has been used for exploring unknown or rare cell types or states in tissues and for elucidating changes in gene expression during differentiation or across time or across states 7 8. Wu et al revealed immune cell heterogeneity in peripheral blood mononuclear cells (PBMCs) of patients with IgG4-RD, and Cai et al described the landscape of T cells and B cells in involved tissue by scRNA-seq 4 9. However, a comprehensive study of the characterisations of all cells in affected tissues and interactions between immune cells and interstitial cells in IgG4-RD remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Wang

Feng

et al. 2023

Ann Rheum Dis

View full text Add to dashboard Cite

ObjectivesThe aim of this study is to profile the transcriptional landscapes of affected tissues and peripheral blood mononuclear cells (PBMCs) at the single-cell level in IgG4-related disease (IgG4-RD). Identifying the cell populations and crosstalk between immune cells and non-immune cells will assist us in understanding the aetiology of IgG4-RD.MethodsWe performed single-cell RNA sequencing analysis on submandibular glands (SMGs) and PBMCs from patients with IgG4-RD and matched controls. Additionally, bulk RNA sequencing of PBMCs was used to construct the immune repertoire. Furthermore, multiplex immunofluorescence staining was performed to validate the transcriptomic results.ResultsWe identified three novel subsets of tissue-resident immune cells in the SMGs of patients with IgG4-RD.TOP2A_B cells andTOP2A_T cells had stemness signatures, and trajectory analysis showed thatTOP2A_B cells may differentiate into IgG4+plasma cells and thatTOP2A_T cells may differentiate into T follicular helper (Tfh) cells.ICOS_PD-1_B cells with Tfh-like characteristics appeared to be an intermediate state in the differentiation from B cells to IgG4+plasma cells. The cellular communication patterns within immune cells and between immune cells and non-immune cells were altered in IgG4-RD compared with controls. Consistently, infection-related pathways were shared in B cells and T cells from SMGs and PBMCs. Furthermore, immune clonotype analysis of PBMC samples showed the complementary determining region 3 amino acid CQQSYSTPYTF was expanded in patients with IgG4-RD.ConclusionOur data revealed the cellular and molecular changes at the single-cell resolution of IgG4-RD and provide valuable insights into the aetiology and novel therapeutic targets of the autoimmune disease.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Wang

Feng

et al. 2023

Ann Rheum Dis

View full text Add to dashboard Cite

show abstract

“…Encouragingly, the T cell receptor signaling pathway, B cell receptor signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation and IL-17 signaling pathway were also displayed in the KEGG enrichment analysis, which are closely correlated with the formation of TLSs. [45][46][47][48][49] Moreover, the major genes for promoting the formation of TLSs (Cxcl13, Lta, Ltb, Tnfsf14, Ccl19, Ccl21a, Ccl21d and Il7r) were detected to be up-regulated. 14,50 The local production of these cytokines could promote lymphoid tissue formation by recruiting B cells or M1 macrophages to the tumor sites, which could bind with adjacent stromal cells by the Lta1b2 and Ltb receptors (LTbR).…”

Section: Tls Formation Facilitated By Zccg Via Dual-pathway Activationmentioning

confidence: 99%

Engineering metal-based hydrogel-mediated tertiary lymphoid structure formation via activation of the STING pathway for enhanced immunotherapy

Jin,

Liang,

Zhang

et al. 2023

Mater. Horiz.

View full text Add to dashboard Cite

show abstract

“…Immunosuppressive agents used in therapy for NS regulate lymphocyte number and function. B-cell-targeting therapies have been the focus of many recent efforts, following the discovery of pathogenic antibodies [ 10 ], but T cells and B cells can interact with each other [ 44 ]. B-cell depletion can indirectly affect T-cell subsets interacting with B cells in lymphoid follicles [ 45 ].…”

Section: Options For Immunosuppressive Agentsmentioning

confidence: 99%

Immunosuppressive Agent Options for Primary Nephrotic Syndrome: A Review of Network Meta-Analyses and Cost-Effectiveness Analysis

Nagai

2023

Medicina

View full text Add to dashboard Cite

Therapeutic options with immunosuppressive agents for glomerular diseases have widened with refinements to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines from 2012 to 2021. However, international guidelines do not necessarily match the reality in each country. Expensive therapies such as rituximab and calcineurin inhibitors are sometimes inaccessible to patients with refractory nephrotic syndrome due to cost or regulations. Under the Japanese medical insurance system, rituximab is accessible but still limited to steroid-dependent patients who developed idiopathic nephrotic syndrome in childhood. Based on international KDIGO guidelines and other national guidelines, possible applications of immunosuppressive agents for nephrotic syndrome are comprehensively examined in this review. While rituximab has become the mainstay of immunosuppressive therapy for nephrotic syndrome, clinical trials have indicated that options such as cyclophosphamide, calcineurin inhibitors, and mycophenolate mofetil would be preferable. Given the rising number of patients with nephrotic syndrome worldwide, KDIGO guidelines mention the need for further consideration of cost-effectiveness. If the new option of rituximab is to be the first choice in combination with steroids for nephrotic syndrome, its cost-effectiveness should also be verified. Among the few studies examining the cost-effectiveness of treatments for nephrotic syndrome, administration of rituximab to young adults has been shown to be cost-beneficial, at least in Japan. However, further large-scale studies involving multiple facilities are needed to verify such findings. Network meta-analyses have concluded that the efficacy of rituximab remains controversial and confirmation through high-quality studies of large cohorts is needed. To this end, the mechanisms of action underlying immunosuppressive agents, both old and new, need to be understood and experience must be accumulated to evaluate possible effects and side effects.

show abstract

The landscape of T and B lymphocytes interaction and synergistic effects of Th1 and Th2 type response in the involved tissue of IgG4-RD revealed by single cell transcriptome analysis

Cited by 13 publications

References 45 publications

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease

Engineering metal-based hydrogel-mediated tertiary lymphoid structure formation via activation of the STING pathway for enhanced immunotherapy

Immunosuppressive Agent Options for Primary Nephrotic Syndrome: A Review of Network Meta-Analyses and Cost-Effectiveness Analysis

Contact Info

Product

Resources

About