Chronic Inflammation: A Common Promoter in Tertiary Lymphoid Organ Neogenesis

Luo, Shanshan; Zhu, Rui; Takata, Yasuyuki; Fan, Huiying; Hu, Yu; Mohanta, Sarajo; Hu, Desheng

doi:10.3389/fimmu.2019.02938

Cited by 55 publications

(41 citation statements)

References 126 publications

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“…The induction of CXCL13 can be locally increased by the transgenic expression of IL-6 and IL-6R forming lymphoid structures in lungs [118]. IL-7 overexpression can also increase the amount of LTi cells in the spleen, pancreas and salivary gland [119]. Furthermore, TLR 1 and 2 ligands (Pam3CSK4) [120] as well as TLR4 ligand (LPS) [121] are also used for TLS genesis in vivo in several mice models of cancers [122].…”

Section: Use Of Cytokines and Chemokines For Tls Neogenesismentioning

confidence: 99%

Tertiary Lymphoid Structures and B cells: Clinical impact and therapeutic modulation in cancer

Sautès-Fridman

Verneau

Sun

et al. 2020

Seminars in Immunology

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Section: Use Of Cytokines and Chemokines For Tls Neogenesismentioning

confidence: 99%

Tertiary Lymphoid Structures and B cells: Clinical impact and therapeutic modulation in cancer

Sautès-Fridman

Verneau

Sun

et al. 2020

Seminars in Immunology

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“…Beside their classical homing function, chemokines such as CCL19, CCL21, CXCL12, and CXCL13 are also implicated, together with cytokines such as IL-17A (enhanced in IL-7treated vaginal mucosa sampled 2 days following the administration of rs-IL-7gly, Supplementary Figure 2) in the organization of TLS and germinal center formation (68,69). At day 2 following rs-IL-7gly administration, most of the infiltrating immune cells were scattered in the lamina propria but lymphoid aggregates composed of T-cells, B-cells and APCs could also be observed in the vaginal mucosa ( Figure 3A, bottom panels).…”

Section: Discussionmentioning

confidence: 99%

IL-7-Adjuvanted Vaginal Vaccine Elicits Strong Mucosal Immune Responses in Non-Human Primates

Logerot

Figueiredo-Morgado

Charmeteau-De-Muylder

et al. 2021

Front. Immunol.

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Mucosal immune responses are crucial in protecting against pathogens entering through mucosal surfaces. However, due to poor T-cell responsiveness upon mucosal antigenic stimulation, mucosal immunity remains difficult to obtain through vaccines and requires appropriate adjuvants. We previously demonstrated that administered systemically to healthy macaques or locally expressed in the intestinal mucosa of acutely SIV-infected macaques, interleukin-7 (IL-7) triggers chemokine expression and immune cell homing into mucosae, suggesting its important role in the development of mucosal immune responses. We therefore examined whether local delivery of recombinant glycosylated simian IL-7 (rs-IL-7gly) to the vaginal mucosa of rhesus macaques could prepare the lower female genital tract (FGT) for subsequent immunization and act as an efficient mucosal adjuvant. First, we showed that local administration of rs-IL-7gly triggers vaginal overexpression of chemokines and infiltration of mDCs, macrophages, NKs, B- and T-cells in the lamina propria while MamuLa-DR+ APCs accumulated in the epithelium. Subsequent mucosal anti-DT immunization in macaques resulted in a faster, stronger, and more persistent mucosal antibody response compared to DT-immunization alone. Indeed, we detected robust productions of DT-specific IgAs and IgGs in their vaginal secretions and identified cells secreting DT-specific IgAs in their vaginal mucosa and IgGs in draining lymph nodes. Finally, the expression of chemokines involved in the organization of tertiary lymphoid structures (TLS) was only increased in the vaginal mucosa of IL-7-adjuvanted immunized macaques. Interestingly, TLSs developed around PNAd+ high endothelial venules in their lower FGT sampled 2 weeks after the last immunization. Non-traumatic vaginal administration of rs-IL-7gly prepares the mucosa to respond to subsequent local immunization and allows the development of a strong mucosal immune response in macaques, through the chemokine-dependent recruitment of immune cells, the activation of mDCs and the formation of TLSs. The localization of DT-specific IgA+ plasma cells in the upper vaginal mucosa argues for their contribution to the production of specific immunoglobulins in the vaginal secretions. Our results highlight the potential of IL-7 as a potent mucosal adjuvant to stimulate the FGT immune system and elicit vaginal antibody responses to local immunization, which is the most promising way to confer protection against many sexually transmitted diseases.

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“…The formation of TLOs is also observed in target organs of autoimmune disease, transplanted organs, solid tumors and chronic inflammation tissues (see the review by Luo et al . 50 ). In human renal allograft rejection, TLO formation in grafts is dependent on IL‐21 51 .…”

Section: Discussionmentioning

confidence: 99%

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

Gassen

Fazolo

Freitas

et al. 2020

Immunol. Cell Biol.

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Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children under 1 year. RSV vaccines are currently unavailable, and children suffering from multiple reinfections by the same viral strain fail to develop protective responses. Although RSV‐specific antibodies can be detected upon infection, these have limited neutralizing capacity. Follicular helper T (Tfh) cells are specialized in providing signals to B cells and help the production and affinity maturation of antibodies, mainly via interleukin (IL) 21 secretion. In this study, we evaluated whether RSV could inhibit Tfh responses. We observed that Tfh cells fail to upregulate IL‐21 production upon RSV infection. In the lungs, RSV infection downregulated the expression of IL‐21/interleukin‐21 receptor (IL‐21R) in Tfh cells and upregulated programmed death‐ligand 1 (PD‐L1) expression in dendritic cells (DCs) and B cells. PD‐L1 blockade during infection recovered IL‐21R expression in Tfh cells and increased the secretion of IL‐21 in a DC‐dependent manner. IL‐21 treatment decreased RSV viral load and lung inflammation, inducing the formation of tertiary lymphoid organs in the lung. It also decreased regulatory follicular T cells, and increased Tfh cells, B cells, antibody avidity and neutralization capacity, leading to an overall improved anti‐RSV humoral response in infected mice. Passive immunization with purified immunoglobulin G from IL‐21‐treated RSV‐infected mice protected against RSV infection. Our results unveil a pathway by which RSV affects Tfh cells by increasing PD‐L1 expression on antigen‐presenting cells, highlighting the importance of an IL‐21–PD‐L1 axis for the generation of protective responses to RSV infection.

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Chronic Inflammation: A Common Promoter in Tertiary Lymphoid Organ Neogenesis

Cited by 55 publications

References 126 publications

Tertiary Lymphoid Structures and B cells: Clinical impact and therapeutic modulation in cancer

Tertiary Lymphoid Structures and B cells: Clinical impact and therapeutic modulation in cancer

IL-7-Adjuvanted Vaginal Vaccine Elicits Strong Mucosal Immune Responses in Non-Human Primates

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

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