Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Objectives: T peripheral helper (Tph) cells have major roles in pathological processes in SLE. We sought to clarify the mechanisms of Tph cell differentiation and their relevance to clinical features in patients with SLE.
Method: Phenotypes and functions of Tph cell-related markers in human CD4+ T cells purified from volunteers or patients were analysed using flow cytometry and quantitative PCR. Renal biopsy specimens from patients with LN were probed by multicolour immunofluorescence staining.
Results: Among multiple cytokines, transforming growth factor (TGF)-β3 characteristically induced programmed cell death protein 1 (PD-1)hi musculoaponeurotic fibrosarcoma (MAF)+, IL-21+IL-10+ Tph-like cells with a marked upregulation of related genes including PDCD-1, MAF, SOX4 and CXCL13. The induction of Tph-like cells by TGF-β3 was suppressed by the neutralization of TGF-β type II receptor (TGF-βR2). TGF-β3-induced Tph-like cells efficiently promoted the differentiation of class-switch memory B cells into plasmocytes, resulting in enhanced antibody production. The proportion of Tph cells in the peripheral blood was significantly increased in patients with SLE than in healthy volunteers in concordance with disease activity and severity of organ manifestations such as LN. TGF-β3 was strongly expressed on macrophages, which was associated with the accumulation of CD4+ C-X-C chemokine receptor (CXCR5)-PD-1+ Tph cells, in the renal tissue of patients with active LN.
Conclusion: The induction of Tph-like cells by TGF-β3 mainly produced from tissue macrophages plays a pivotal role in the pathological processes of active LN by enhancing B-cell differentiation in patients with SLE.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/rheumatology/keac646 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Comprehensive and advanced T cell cluster analysis for discriminating seropositive and seronegative rheumatoid arthritis.
Front Immunol
August 2025
Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Objective: Rheumatoid arthritis (RA) is classified into seropositive (SP-RA) and seronegative (SN-RA) types, reflecting distinct immunological profiles. This study aimed to identify the T cell phenotypes associated with each type, thereby enhancing our understanding of their unique pathophysiological mechanisms.
Methods: We analyzed peripheral blood T cells from 50 participants, including 16 patients with untreated SP-RA, 17 patients with SN-RA, and 17 healthy controls, utilizing 25 T cell markers.
Follicular helper- and peripheral helper-like T cells drive autoimmune disease in human immune system mice.
Elife
April 2025
Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, Columbia University, New York, United States.
Human immune system (HIS) mice constructed in various ways are widely used for investigations of human immune responses to pathogens, transplants, and immunotherapies. In HIS mice that generate T cells de novo from hematopoietic progenitors, T cell-dependent multisystem autoimmune disease occurs, most rapidly when the human T cells develop in the native NOD.Cg- scid tm1Wjl (NSG) mouse thymus, where negative selection is abnormal.
View Article and Find Full Text PDFHomeostatic signals, including IL-7 and self-MHC recognition, induce the development of peripheral helper T cells, which are enriched in the joints of rheumatoid arthritis.
J Transl Autoimmun
December 2024
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Objective: Dysregulated T cell homeostasis has long been implicated in the pathogenesis of rheumatoid arthritis (RA), in the joint of which peripheral helper T (Tph) cells accumulate and form ectopic lymphoid organs. We examined whether homeostatic signals are involved in the development of Tph cells.
Methods: Human peripheral blood mononuclear cells were cultured with IL-7, the critical cytokine for T cell homeostasis.
Myelin-reactive B cells exacerbate CD4 T cell-driven CNS autoimmunity in an IL-23-dependent manner.
Nat Commun
June 2024
axe Neurosciences, Centre de recherche du Centre hospitalier universitaire (CHU) de Québec - Université Laval, Pavillon CHUL, 2705 boul Laurier, Quebec City, G1V 4G2, QC, Canada.
B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein (MOG). Here, we show that upon immunization with the T cell-obligate autoantigen, MOG, IgH mice develop rapid and exacerbated experimental autoimmune encephalomyelitis (EAE) relative to wildtype (WT) counterparts, characterized by aggregation of T and B cells in the IgH meninges and by CD4 T helper 17 (Th17) cells in the CNS.
View Article and Find Full Text PDFArticle Synopsis
- Human immune system (HIS) mice are used to study how human immune responses work, especially in relation to diseases and treatments.
- The study finds that T cells from different thymus sources contribute differently to autoimmune diseases, with those developing in a mouse thymus causing faster disease onset compared to those from a human thymus.
- Specific helper-like T cells (Tph and Tfh) were shown to induce autoimmune responses, highlighting their role and pointing towards future research on treating human autoimmune diseases.