Tonsillitis exacerbates renal injury in IgA nephropathy through promoting Th22 cells chemotaxis

Gan, Lu; Zhu, Mengyuan; Li, Xiaozhao; Chen, Chen; Meng, Ting; Pu, Jiaxi; Luo, Hui-ming; Shao, Fengmin; Zhou, Qiaoling

doi:10.1007/s11255-018-1792-2

Cited by 11 publications

(9 citation statements)

References 24 publications

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“…Moreover, Th2 polarization might intensify the response of glomerular cells to IgA immune complexes and both directly and indirectly decrease glomerular filtration rate (GFR) [49]. Gan et al confirmed higher renal expression of CCL20, CCL22, and CCL27 in IgAN patients; the elevation was even more pronounced in patients with accompanying tonsillitis [16]. Moreover, elevation of Th22 cells in patients’ peripheral blood was associated with worse histologic renal images; the percentage of Th22 cells was positively correlated with MEST scores.…”

Section: Renal Injury—th2 Th17 Th22 and Treg Cells Participation Inmentioning

confidence: 99%

“…Moreover, elevation of Th22 cells in patients’ peripheral blood was associated with worse histologic renal images; the percentage of Th22 cells was positively correlated with MEST scores. Authors concluded that tonsillitis aggravated renal injury in IgAN through induction of Th22 lymphocytosis, infiltration of renal tissue, and promotion of renal fibrosis by Th22 [16, 76].…”

Section: Renal Injury—th2 Th17 Th22 and Treg Cells Participation Inmentioning

confidence: 99%

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T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

et al. 2018

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Background Immunoglobulin A nephropathy (IgAN), the most frequent cause of primary glomerulonephritis worldwide, is an autoimmune disease with complex pathogenesis. In this review, we focus on T cells and summarize knowledge about their involvement in pathophysiology and treatment of IgAN Methods We reviewed the literature for (1) alterations of T cell subpopulations in IgAN, (2) experimental and clinical proofs for T cells’ participation in IgAN pathogenesis, (3) clinical correlations with T cell-associated alterations, and (4) influence of drugs used in IgAN therapy on T cell subpopulations. Results We found that IgAN is characterized by higher proportions of circulatory Th2, Tfh, Th17, Th22 and γδ T cells, but lower Th1 and Treg cells. We discuss genetic and epigenetic makeup that may contribute to this immunological phenotype. We found that Th2, Th17 and Tfh-type interleukins contribute to elevated synthesis of galactose-deficient IgA1 (Gd-IgA1) and that the production of anti-Gd-IgA1 autoantibodies may be stimulated by Tfh cells. We described the roles of Th2, Th17, Th22 and Treg cells in the renal injury and summarized correlations between T cell-associated alterations and clinical features of IgAN (proteinuria, reduced GFR, hematuria). We detailed the impact of immunosuppressive drugs on T cell subpopulations and found that the majority of drugs have nonoptimal influence on T cells in IgAN patients. Conclusions T cells play an important role in IgAN pathogenesis and are correlated with its clinical severity. Clinical trials with the drugs targeting the reported alterations of the T-cell compartment are highly desirable.

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Section: Renal Injury—th2 Th17 Th22 and Treg Cells Participation Inmentioning

confidence: 99%

Section: Renal Injury—th2 Th17 Th22 and Treg Cells Participation Inmentioning

confidence: 99%

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

et al. 2018

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Section: Introductionmentioning

confidence: 99%

“…Our research group demonstrated that CD4 + T lymphocytes, a crucial component of the mucosal immune system that can defend against pathogens, play a key role in IgAN development (Meng et al, 2014; Xiao et al, 2016; Gan et al, 2018b). Increased frequencies of Th17 cells and Th22 cells and decreased Treg frequencies in blood and kidney were observed in IgAN mice compared to normal mice (Meng et al, 2014; Gan et al, 2018b). Moreover, the imbalances in Th17 and Treg cells were further disturbed in mice with IgA nephropathy by hemolytic streptococcus infection (Meng et al, 2014) and tonsillitis (Gan et al, 2018b), respectively.…”

Section: Introductionmentioning

confidence: 99%

Respiratory Syncytial Virus Exacerbates Kidney Damages in IgA Nephropathy Mice via the C5a-C5aR1 Axis Orchestrating Th17 Cell Responses

Feng

Zhou

et al. 2019

Front. Cell. Infect. Microbiol.

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Respiratory viral infections can directly lead to kidney damage such as IgA nephropathy (IgAN), partly due to mucosal immune system dysfunction. Although the activated C5a-C5aR1 axis results in increased Th1 and Th17 frequencies but reduced Treg frequencies in Respiratory syncytial virus (RSV) infection, how this axis affects Th cell disorders in RSV-induced IgAN exacerbation remains unknown. Here, we used a mouse model to dissect the activation of C5a-C5aR1 by RSV and the consequences on the regulation of Th1, Th17, and Treg immune responses in IgA nephropathy. RSV fusion protein was clearly deposited not only in the pulmonary interstitium but also in the glomerulus in RSV-IgAN mice, and RSV infection led to more severe pathological changes in the kidneys in IgAN mice. Blocking the C5a-C5aR1 axis resulted in a decrease in the albumin-to-creatinine ratio, and the attenuation of kidney damage in IgAN and RSV-IgAN mice might be partly attributed to the inhibition of Th cell and cytokine dysfunction. Th1, Th17 and Treg immune responses and their corelative cytokines were disrupted by RSV infection and rescued by C5aR1 inhibition. Moreover, we constructed a coculture system of human mesangial cells and CD4 + T cells and found that RSV infection might lead to CD4 + T cell production via human mesangial cells-enhanced CD4 + T cell proliferation, consequently increasing IL-17 levels. These pathological behaviors were augmented by C5a stimulation and decreased by C5aR1 inhibition. Thus, C5aR1 inhibition alters both kidney damage and Th1, Th17, and Treg cell dysfunction in RSV-induced IgAN exacerbation and locally regulates HMC antigen presentation function in the kidney. Taken together, our data offer profound evidence that blocking the C5a-C5aR1 axis might be a potential therapy for RSV-induced IgAN.

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“…The efficacy of tonsillectomy for IgAN has been clinically shown by a recent randomized controlled trials, 52 and it has also been published as a recommended treatment in IgAN clinical practice guidelines. 4 Recently, scientific evidence supporting the use of tonsillectomy has gradually accumulated, and this treatment is being developed not only in Asia 53,54 but also in Europe and the United States. 30,55 We hope that many additional researchers will publish new evidence linking the tonsils and kidneys in the future.…”

Section: Discussionmentioning

confidence: 99%

Recent advances in the immunological understanding of association between tonsil and immunoglobulin A nephropathy as a tonsil‐induced autoimmune/inflammatory syndrome

Harabuchi

Takahara

2019

Immunity Inflam & Disease

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Introduction Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. It is well known that upper respiratory tract infections, particularly acute tonsillitis, often worsen IgAN. Recent many clinical studies clearly show that tonsillectomy with steroid pulse therapy is the effective treatments for IgAN patients. Recently, the immunological evidence of association between tonsil and IgAN has been reported. Methods In this review, the mechanism underlying the onset of IgAN, as a tonsil‐induced autoimmune/inflammatory syndrome (TIAS), is outlined with the main focus on the authors' research results. Results In the tonsils of patients with IgAN, hyperimmune response to the unmethylated deoxycytidyl‐deoxyguanosine oligodeoxynucleotides (CpG‐ODN) take place, resulting in hyperproduction of interferon‐γ. The hyperproduction is followed by both overproduction of mutated IgA via B‐cell activating factor (BAFF)/a proliferation‐inducing ligand (APRIL)‐mediated pathways and overexpression of T‐cell receptor Vβ6, CXCR3, and CX3CR1 on tonsillar T cells. These IgA and T cells home to the kidney via the systemic circulation, resulting in nephritis of IgAN. Conclusions Scientific evidence supporting the use of tonsillectomy has gradually accumulated. We hope that many additional researchers will publish new evidence linking the tonsils and kidneys in the future.

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Tonsillitis exacerbates renal injury in IgA nephropathy through promoting Th22 cells chemotaxis

Abstract: Tonsil infection may aggravate the renal pathological lesions of IgAN by exacerbating Th22 cell accumulation. Our data suggested a collaboration between HMC and Th22 cells in IgAN with tonsillitis underlying the effects of CCL20, CCL22, and CCL27.

Cited by 11 publications

References 24 publications

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

Respiratory Syncytial Virus Exacerbates Kidney Damages in IgA Nephropathy Mice via the C5a-C5aR1 Axis Orchestrating Th17 Cell Responses

Recent advances in the immunological understanding of association between tonsil and immunoglobulin A nephropathy as a tonsil‐induced autoimmune/inflammatory syndrome

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