IL‐21 treatment recovers follicular helper T cells and neutralizing antibody production in respiratory syncytial virus infection

Gassen, Rodrigo Benedetti; Fazolo, Tiago; Freitas, Deise Nascimento de; Borges, Thiago J.; Lima, Karina; Antunes, Géssica Luana; Maito, Fábio Luiz Dal Moro; Mendes, Daniel Ag Bueno; Báfica, André; Rodrigues, Luiz Carlos; Stein, Renato T.; Souza, Ana Paula Duarte de; Bonorino, Cristina

doi:10.1111/imcb.12418

Cited by 10 publications

(14 citation statements)

References 69 publications

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“…Finally, PD-1 and PD-L1 expression on B cells was described to be upregulated by in vitro stimulation with Helicobacter and to mediate Tr1 differentiation ( 456 ). Moreover, PD-L1 upregulation on B cells, associated with T cell exhaustion, was observed in RSV-infected mice ( 457 ) and HIV-infected patients ( 455 ), suggesting a role for PD-L1 + Bregs as a mechanism to limit tissue damage that can be subverted by pathogens in their benefit.…”

Section: Suppressive Mechanisms Of Bregs By Cell Surface-expressed Moleculesmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory B Cells

et al. 2021

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Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.

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Section: Suppressive Mechanisms Of Bregs By Cell Surface-expressed Moleculesmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory B Cells

et al. 2021

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“…Scrutiny of TLS induction in non-tumor bearing animal models has provided with crucial information for the understanding of the complex, tightly regulated, non-redundant mechanisms that lead to initiation, formation and maintenance of these lymphoid ectopic structures (55). Notably, several recent reports have shed new light in the ontogeny of TLS in mouse models of lung disorders (33,(60)(61)(62)(63)(64)(65)(66). In a model of viral infection with respiratory syncytial virus (RSV), Gassen et al reported a RSVdependent down-modulation of both IL-21 and IL-21R expression by lung Tfh cells, accompanied by an up-regulation of PD-L1 expression on resident B cells and DC, resulting in a defective GC formation and anti-RSV antibody response.…”

Section: Learning From Tls Study In Non-tumor Inflammatory Diseases To Better Understand Tls Role In Cancermentioning

confidence: 99%

“…Therapeutic blockade of PD‐L1 restored IL‐21R expression and increased IL‐21 secretion by Tfh cells. In parallel, treatment of RSV-infected mice with IL‐21 decreased the viral load and inflammation, while inducing the formation of TLS and improving the antibody response against RSV in the lung of infected animals ( 60 ). These results highlight the complex interplay between the IL‐21/IL‐21R and the PD‐1/PD‐L1 axes leading to the regulation of Tfh function and TLS formation in RSV-infected lungs.…”

Section: Learning From Tls Study In Non-tumor Inflammatory Diseases To Better Understand Tls Role In Cancermentioning

confidence: 99%

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

et al. 2021

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The tumor microenvironment is a complex ecosystem almost unique to each patient. Most of available therapies target tumor cells according to their molecular characteristics, angiogenesis or immune cells involved in tumor immune-surveillance. Unfortunately, only a limited number of patients benefit in the long-term of these treatments that are often associated with relapses, in spite of the remarkable progress obtained with the advent of immune checkpoint inhibitors (ICP). The presence of “hot” tumors is a determining parameter for selecting therapies targeting the patient immunity, even though some of them still do not respond to treatment. In human studies, an in-depth analysis of the organization and interactions of tumor-infiltrating immune cells has revealed the presence of an ectopic lymphoid organization termed tertiary lymphoid structures (TLS) in a large number of tumors. Their marked similarity to secondary lymphoid organs has suggested that TLS are an “anti-tumor school” and an “antibody factory” to fight malignant cells. They are effectively associated with long-term survival in most solid tumors, and their presence has been recently shown to predict response to ICP inhibitors. This review discusses the relationship between TLS and the molecular characteristics of tumors and the presence of oncogenic viruses, as well as their role when targeted therapies are used. Also, we present some aspects of TLS biology in non-tumor inflammatory diseases and discuss the putative common characteristics that they share with tumor-associated TLS. A detailed overview of the different pre-clinical models available to investigate TLS function and neogenesis is also presented. Finally, new approaches aimed at a better understanding of the role and function of TLS such as the use of spheroids and organoids and of artificial intelligence algorithms, are also discussed. In conclusion, increasing our knowledge on TLS will undoubtedly improve prognostic prediction and treatment selection in cancer patients with key consequences for the next generation immunotherapy.

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“…RSV inhibited the humoral immune response of B cells by negatively regulating the expression of IL-21R on the surface of T follicular helper (TFH) cells and IL-21 in immature B cells. These findings may explain the lack of an immune response [72]. In infants with severe respiratory tract infection, the production of IFN-γ by NK cells induced by specific antibodies to RSV was significantly lower than that in uninfected infants, and the activation of these NK cells seemed to be related to Fc fucosylation of RSV-specific antibodies [73].…”

Section: Pathogenesismentioning

confidence: 93%

Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

Shang¹,

Tan²,

Ma³

2021

Int. J. Biol. Sci.

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Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. It has been more than 60 years since RSV was discovered, and the palivizumab monoclonal antibody, the only approved specific treatment, is limited to use for passive immunoprophylaxis in high-risk infants; no other intervention has been approved to date. However, in the past decade, substantial progress has been made in characterizing the structure and function of RSV components, their interactions with host surface molecules, and the host innate and adaptive immune response to infection. In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. A large number of promising monoclonal antibodies and inhibitors have been screened, and new vaccine candidates have been designed for clinical evaluation. In this review, we first briefly introduce the structural composition, host cell surface receptors and life cycle of RSV virions. Then, we discuss the latest findings related to the pathogenesis of RSV. We also focus on the latest clinical progress in the prevention and treatment of RSV infection through the development of monoclonal antibodies, vaccines and small-molecule inhibitors. Finally, we look forward to the prospects and challenges of future RSV research and clinical intervention.

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IL‐21 treatment recovers follicular helper T cells and neutralizing antibody production in respiratory syncytial virus infection

Cited by 10 publications

References 69 publications

Immunosuppressive Mechanisms of Regulatory B Cells

Immunosuppressive Mechanisms of Regulatory B Cells

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

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