Follicular helper T (Tfh) cells contribute to various immune responses as well as to the pathogenesis of several immune diseases. However, the precise mechanism underlying the onset or development of autoimmunity via Tfh cells remains unclear. Herein, the detailed relationship between autoimmune disease and Tfh cells was analyzed using a murine model for Sjögren syndrome (SS) wherein the mice underwent neonatal thymectomy. Germinal center (GC) development was promoted in this SS model along with an increase of Tfh cells and GC B cells. The severity of the autoimmune lesions was correlated with the number of Tfh cells detected in the spleen of the SS model mice. In addition, treatment with an anti-CD20 monoclonal antibody effectively suppressed the autoimmune lesions with a reduction of Tfh cells and GC B cells. Comprehensive gene analysis revealed that several genes associated with Tfh cell differentiation, including achaete-scute homologue 2 (Ascl2), were up-regulated in peripheral CD25 CD4 T cells in SS model mice compared with those in control mice. Moreover, an experiment using CD4Bcl6 mice that received neonatal thymectomy treatment demonstrated that Ascl2 contributes to the Tfh cell differentiation associated with autoimmunity during the early stages, independent of Bcl6. In conclusion, our results indicate that abnormal Tfh cell differentiation via Ascl2 regulation might contribute to the pathogenesis of autoimmunity.
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http://dx.doi.org/10.1016/j.ajpath.2019.08.008 | DOI Listing |
Cell Biol Toxicol
December 2024
Department of Rheumatology and Immunology, The First Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
The autoimmune disorder known as Systemic Lupus Erythematosus (SLE) exhibits intricate features with abnormal immune responses leading to tissue injury. The generation of antibodies and the disruption of immune regulation heavily depend on the pivotal function of T follicular helper (Tfh) cells. Iron dysregulation is significant in autoimmune diseases, impacting immune cell function and disease progression.
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December 2024
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Increased antibody affinity over time after vaccination, known as affinity maturation, is a prototypical feature of immune responses. Recent studies have shown that a diverse collection of B cells, producing antibodies with a wide spectrum of different affinities, are selected into the plasma cell (PC) pathway. How affinity-permissive selection enables PC affinity maturation remains unknown.
View Article and Find Full Text PDFBlood Cancer J
December 2024
Lymphoma Center, Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Angioimmunoblastic T-cell lymphoma (AITL) is a kind of aggressive T-cell lymphoma with significant enrichment of non-malignant tumor microenvironment (TME) cells. However, the complexity of TME in AITL progression is poorly understood. We performed single-cell RNA-Seq (scRNA-seq) and imaging mass cytometry (IMC) analysis to compare the cellular composition and spatial architecture between relapsed/refractory AITL (RR-AITL) and newly diagnosed AITL (ND-AITL).
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December 2024
Sorbonne Université, INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy, i3, Paris, France.
J Virol
December 2024
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Unlabelled: During activation, the T cell transmembrane receptor CD6 becomes incorporated into the T cell immunological synapse where it can exert both co-stimulatory and co-inhibitory functions. Given the ability of CD6 to carry out opposing functions, this study sought to determine how CD6 regulates early T cell activation in response to viral infection. Infection of CD6-deficient mice with a neurotropic murine coronavirus resulted in greater activation and expansion of CD4 T cells in the draining lymph nodes.
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