Th17 Cells Facilitate the Humoral Immune Response in Patients with Acute Viral Myocarditis

Yuan, Jing; Cao, Axiu; Yu, Miao; Lin, Qiong-Wen; Lei, Yu; Zhang, Jinghui; Wang, Min; Guo, Hao; Liao, Yuhua

doi:10.1007/s10875-009-9355-z

Cited by 64 publications

(55 citation statements)

References 25 publications

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“…Besides the proinflammatory effect of Th17 cells, our earlier research suggested that Th17 cells could facilitate the production of autoantibodies in the development of AVMC (5,6). However, the relationship between Th17 cells and CVB3 replication remains unknown in AVMC.…”

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confidence: 97%

Th17 Cells Contribute to Viral Replication in Coxsackievirus B3-Induced Acute Viral Myocarditis

Yuan¹,

Yu²,

Lin³

et al. 2010

The Journal of Immunology

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Acute viral myocarditis (AVMC) is characterized by virus-triggered myocardial inflammation, and Coxsackievirus B3 (CVB3) is the primary pathogen. We previously proved that Th17 cells, besides having proinflammatory effects, were involved in AVMC by enhancing humoral response. However, the relationship between Th17 cells and CVB3 replication remains unknown. In this experiment, we infected BALB/c mice with CVB3 for establishing AVMC models and then found that, with the increase of viral replication, the expressions of splenic Th17 cells, serum IL-17, and cardiac IL-17 mRNA were elevated significantly, accompanied by the progressive cardiac injuries of AVMC. Furthermore, on day 5, the peak time for viral replication, correlation was positive between cardiac IL-17 mRNA and CVB3 RNA (correlation index = 0.835; p < 0.01). Although the expressions of Th1 and CD8+ T cells, which could secrete the antiviral cytokine IFN-γ and damage the heart, were also elevated, along with Th17 cells, in AVMC, the neutralization of IL-17 further upregulated the percentages of splenic Th1 and CD8+ T cells and the levels of cardiac IFN-γ mRNA. The cardiac pathological changes were obviously improved after neutralization, with reduced viral replication followed by decreases in the cardiac inflammatory cytokines IL-17, TNF-α, and IL-1β. These data suggest that Th17 cells contribute to CVB3 replication in AVMC, and that IL-17 might be an important target for regulating the balance of antiviral immunities.

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confidence: 97%

Th17 Cells Contribute to Viral Replication in Coxsackievirus B3-Induced Acute Viral Myocarditis

Yuan¹,

Yu²,

Lin³

et al. 2010

The Journal of Immunology

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“…Our previous studies demonstrated that the blockade of the MR blunts the ability of aldosterone to induce Th17 polarization in vitro 22 and MR blockade reduced myocardial fibrosis and enhanced survival of mice with viral myocarditis, a Th17-associated disease. 26,27 Even though IL-17 blockade (protocol 3) ameliorated hypertension, oxidative stress, and fibrosis, we observed that the antihypertensive triple therapy prevented glomerular damage and cardiac hypertrophy in DOCA-salt rats, indicating that development of renal dysfunction and cardiac hypertrophy are blood pressure dependent. The induction of Foxp3 expression in T cells results in a strong reduction of Th17 polarization and blunts the RORγt-induced expression of IL-17 both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 78%

Spironolactone Decreases DOCA–Salt–Induced Organ Damage by Blocking the Activation of T Helper 17 and the Downregulation of Regulatory T Lymphocytes

et al. 2014

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Adaptive immune response has been implicated in inflammation and fibrosis as a result of exposure to mineralocorticoids and a high-salt diet. We hypothesized that in mineralocorticoid-salt–induced hypertension, activation of the mineralocorticoid receptor alters the T-helper 17 lymphocyte (Th17)/regulatory T-lymphocyte/interleukin-17 (IL-17) pathway, contributing to cardiac and renal damage. We studied the inflammatory response and tissue damage in rats treated with deoxycorticosterone acetate and high-salt diet (DOCA–salt), with or without mineralocorticoid receptor inhibition by spironolactone. To determine whether Th17 differentiation in DOCA–salt rats is caused by hypertension per se, DOCA–salt rats received antihypertensive therapy. In addition, to evaluate the pathogenic role of IL-17 in hypertension and tissue damage, we studied the effect of IL-17 blockade with a specific antibody (anti–IL-17). We found activation of Th17 cells and downregulation of forkhead box P3 mRNA in peripheral tissues, heart, and kidneys of DOCA–salt–treated rats. Spironolactone treatment prevented Th17 cell activation and increased numbers of forkhead box P3–positive cells relative to DOCA–salt rats. Antihypertensive therapy did not ameliorate Th17 activation in rats. Treatment of DOCA–salt rats with anti–IL-17 significantly reduced arterial hypertension as well as expression of profibrotic and proinflammatory mediators and collagen deposits in the heart and kidney. We conclude that mineralocorticoid receptor activation alters the Th17/regulatory T-lymphocyte/IL-17 pathway in mineralocorticoid-dependent hypertension as part of an inflammatory mechanism contributing to fibrosis.

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“…Although the role of IL-17A in humoral immunity is not well understood, it has been shown that B cells express IL-17RA (59), whereas Th17 cells (major IL-17A producers) promote antibody production by B cells (60). To test the possible effect of IL-17A in humoral immune responses during WNV infection, we compared WNV-Especific IgM antibody production in WNV-infected Il17a Ϫ/Ϫ and WT mice by ELISA.…”

Section: Figmentioning

confidence: 99%

Interleukin-17A Promotes CD8⁺T Cell Cytotoxicity To Facilitate West Nile Virus Clearance

Acharya

Wang

Paul

et al. 2017

J Virol

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CD8 ϩ T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8 ϩ T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a Ϫ/Ϫ ) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8 ϩ T cells isolated from Il17a Ϫ/Ϫ mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in vivo. Importantly, treatment of WNV-infected mice with recombinant IL-17A, as late as day 6 postinfection, significantly reduces the viral burden and increases survival, suggesting a therapeutic potential for IL-17A. In conclusion, we report a novel function of IL-17A in promoting CD8 ϩ T cell cytotoxicity, which may have broad implications in other microbial infections and cancers.IMPORTANCE Interleukin-17A (IL-17A) and CD8 ϩ T cells regulate diverse immune functions in microbial infections, malignancies, and autoimmune diseases. IL-17A is a proinflammatory cytokine produced by diverse cell types, while CD8 ϩ T cells (known as cytotoxic T cells) are major cells that provide immunity against intracellular pathogens. Previous studies have demonstrated a crucial role of CD8 ϩ T cells in recovery from West Nile virus (WNV) infection. However, the role of IL-17A during WNV infection remains unclear. Here, we demonstrate that IL-17A protects mice from lethal WNV infection by promoting CD8 ϩ T cell-mediated clearance of WNV. In addition, treatment of WNV-infected mice with recombinant IL-17A reduces the viral burden and increases survival of mice, suggesting a potential therapeutic. This novel IL-17A-CD8 ϩ T cell axis may also have broad implications for immunity to other microbial infections and cancers, where CD8 ϩ T cell functions are crucial.

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Th17 Cells Facilitate the Humoral Immune Response in Patients with Acute Viral Myocarditis

Abstract: It was Th17 cells but not Th2 cells that helped the B cells to produce AHA in AVMC and not until at the late phase of viral myocarditis could Th2 cells play the important role in mediating humoral response.

Cited by 64 publications

References 25 publications

Th17 Cells Contribute to Viral Replication in Coxsackievirus B3-Induced Acute Viral Myocarditis

Th17 Cells Contribute to Viral Replication in Coxsackievirus B3-Induced Acute Viral Myocarditis

Spironolactone Decreases DOCA–Salt–Induced Organ Damage by Blocking the Activation of T Helper 17 and the Downregulation of Regulatory T Lymphocytes

Interleukin-17A Promotes CD8⁺T Cell Cytotoxicity To Facilitate West Nile Virus Clearance

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Th17 Cells Facilitate the Humoral Immune Response in Patients with Acute Viral Myocarditis

Abstract: It was Th17 cells but not Th2 cells that helped the B cells to produce AHA in AVMC and not until at the late phase of viral myocarditis could Th2 cells play the important role in mediating humoral response.

Cited by 64 publications

References 25 publications

Th17 Cells Contribute to Viral Replication in Coxsackievirus B3-Induced Acute Viral Myocarditis

Th17 Cells Contribute to Viral Replication in Coxsackievirus B3-Induced Acute Viral Myocarditis

Spironolactone Decreases DOCA–Salt–Induced Organ Damage by Blocking the Activation of T Helper 17 and the Downregulation of Regulatory T Lymphocytes

Interleukin-17A Promotes CD8+T Cell Cytotoxicity To Facilitate West Nile Virus Clearance

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Interleukin-17A Promotes CD8⁺T Cell Cytotoxicity To Facilitate West Nile Virus Clearance