1IFN-α Modulates Memory Tfh Cells and Memory B Cells in Mice, Following Recombinant FMDV Adenoviral Challenge

Duan, Xiangguo; Sun, Peng; Lan, Yaru; Shen, Chunxiu; Zhang, Xiaoyu; Hou, Shaozhang; Chen, Jian; Ma, Bin; Xia, Yuhan; Su, Chunxia

doi:10.3389/fimmu.2020.00701

Cited by 11 publications

(11 citation statements)

References 33 publications

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“…IL-4 acts as both an inducing factor and an effector molecule of Tfh2 cells as IL-4 neutralization significantly decreased the frequencies of Tfh2 cells in SLE mice while alleviating splenomegaly and reducing IgE autoantibody titers in SLE mice ( 26 ). In addition to IL-4, interferon-α (IFN-α) is also described to enhance the generation of circulatory Tfh2 cells in a model of adenovirus infection ( 56 ). The primary function of Tfh2 cells is the induction of IgE.…”

Section: Induction Phasementioning

confidence: 99%

T Helper 2-Associated Immunity in the Pathogenesis of Systemic Lupus Erythematosus

Kim

2022

Front. Immunol.

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Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that mainly affects women in their reproductive years. A complex interaction of environmental and genetic factors leads to the disruption of immune tolerance towards self, causing overt immune activation and production of autoantibodies that attack multiple organs. Kidney damage, termed lupus nephritis, is the leading cause of SLE-related morbidity and mortality. Autoantibodies are central to propagating lupus nephritis through forming immune complexes and triggering complements. Immunoglobulin G (IgG) potently activates complement; therefore, autoantibodies were mainly considered to be of the IgG isotype. However, studies revealed that over 50% of patients produce autoantibodies of the IgE isotype. IgE autoantibodies actively participate in disease pathogenesis as omalizumab treatment, a humanized anti-IgE monoclonal antibody, improved disease severity in an SLE clinical trial. IgE is a hallmark of T helper 2-associated immunity. Thus, T helper 2-associated immunity seems to play a pathogenic role in a subset of SLE patients. This review summarizes human and animal studies that illustrate type 2 immune responses involved during the pathology of SLE.

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Section: Induction Phasementioning

confidence: 99%

T Helper 2-Associated Immunity in the Pathogenesis of Systemic Lupus Erythematosus

Kim

2022

Front. Immunol.

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“…Tfh cells have a direct effect on B cells and facilitate GC formation 13,22 . Aberrant formation of GCs and abnormal number of GCs in B cells, which influence the production of autoantibodies, are also connected with the progression of SLE 13‐15 . Our findings show that the effects of Dex effect on Tfh cells result in an obvious decrease in the frequency of GCs in B cells in mice.…”

Section: Discusionmentioning

confidence: 60%

Section: Discusionmentioning

confidence: 99%

“…Compared to other CD4 + T cells, Tfh cells specifically express the transcription factor BCL‐6 and produce the characteristic cytokine IL‐21 10‐12 . Tfh cells help to generate germinal centre (GC) reactions where somatic hypermutation and affinity maturation occur, leading to the production of memory B cells and plasma cells 13‐15 . Thus, Tfh cells are crucial to GC reactions and high‐affinity antibody production.…”

Section: Introductionmentioning

confidence: 99%

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Dexamethasone reduces autoantibody levels in MRL/lpr mice by inhibiting Tfh cell responses

Shen

Xue

Zhang

et al. 2021

J Cellular Molecular Medi

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Previous studies have shown that dexamethasone (Dex) reduces the levels of anti‐nuclear (ANA) and anti‐dsDNA antibodies in MRL/lpr mice (a mouse model of SLE). However, the effect of Dex on T follicular helper (Tfh) cells is less documented. Here, using the MRL/lpr mouse model, we investigated the influence of Dex on Tfh cells and potential underlying mechanisms. The data showed that the proportion of Tfh cells, identified as CD4+CXCR5+ICOS+, CD4+CXCR5+PD‐1+ or CD4+BCL‐6+ cells, markedly decreased after treatment with the Dex, in both Balb/c mice and MRL/lpr mice. Dex significantly inhibited IL‐21 expression at both the mRNA and the protein levels. Dex also significantly reduced the proportion of germinal centre B cells and decreased serum IgG, IgG2a/b and IgA levels. Moreover, a positive correlation between the proportion of Tfh cells (CD4+CXCR5+ICOS+, CD4+CXCR5+PD‐1+ or CD4+BCL‐6+) and autoantibodies was observed. Dex significantly increased the Prdm1 and Stat5b mRNA expression and decreased the Bcl‐6 and c‐Maf mRNA expression of CD4+T cells. In brief, Dex inhibited the Tfh development, which relies on many other transcription factors in addition to Bcl‐6. Our data indicate that Dex can be used as a Tfh cell inhibitor in SLE.

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“…Use of this molecule with FMD vaccines seems like the perfect therapeutic combination to achieve early full and long-lasting protection. In this regard, IFNα would not only be effective at blocking initial FMDV replication, as demonstrated in this manuscript, but would also be an effective adjuvant for the FMD vaccine, as it has been previously described ( de Avila Botton et al, 2006 ; Su et al, 2013 ; Duan et al, 2020 ). Further studies using the PEGpoIFNα in combination with FMD vaccines to confirm this adjuvant effect are warranted.…”

Section: Discussionmentioning

confidence: 53%

Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV

et al. 2021

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Interferons (IFNs) are considered the first line of defense against viral diseases. Due to their ability to modulate immune responses, they have become an attractive therapeutic option to control virus infections. In fact, like many other viruses, foot-and-mouth disease virus (FMDV), the most contagious pathogen of cloven-hoofed animals, is highly sensitive to the action of IFNs. Previous studies demonstrated that type I, II, and III IFNs, expressed using a replication defective human adenovirus 5 (Ad5) vector, can effectively block FMDV replication in vitro and can protect animals when challenged 1 day after Ad5-IFN treatment, in some cases providing sterile immunity. Rapidly spreading foot-and-mouth disease (FMD) is currently controlled with vaccination, although development of a protective adaptive immune response takes 5–7 days. Therefore, an optimal strategy to control FMD outbreaks is to block virus replication and spread through sustained IFN activity while the vaccine-stimulated adaptive immune response is developed. Challenges with methods of delivery and/or with the relative short IFN protein half-life in vivo, have halted the development of such approach to effectively control FMD in the animal host. One strategy to chemically improve drug pharmacodynamics is the use of pegylation. In this proof-of-concept study, we demonstrate that pegylated recombinant porcine (po)IFNα displays strong and long-lasting antiviral activity against FMDV in vitro and in vivo, completely protecting swine against FMD for at least five days after a single dose. These results highlight the potential of this biotherapeutics to use in combination with vaccines to fully control FMD in the field.

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1IFN-α Modulates Memory Tfh Cells and Memory B Cells in Mice, Following Recombinant FMDV Adenoviral Challenge

Cited by 11 publications

References 33 publications

T Helper 2-Associated Immunity in the Pathogenesis of Systemic Lupus Erythematosus

T Helper 2-Associated Immunity in the Pathogenesis of Systemic Lupus Erythematosus

Dexamethasone reduces autoantibody levels in MRL/lpr mice by inhibiting Tfh cell responses

Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV

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