The epipharynx-kidney axis triggers glomerular vasculitis in immunoglobulin A nephropathy

Hasegawa, Osamu; Oda, Takashi

doi:10.1007/s12026-019-09099-3

Cited by 7 publications

(7 citation statements)

References 56 publications

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“…Regarding the underlying mechanism of synpharyngitic gross hematuria, we have proposed the concept of “epipharynx–kidney axis” [ 55 ]. Given that epipharyngeal T cells, as part of MALT, may behave similarly to tonsillar interfollicular T cells, namely, enhanced expression of CX3CR1 in CD8+T cells and other CXCR1+ cells, we postulate that upregulation of fractalkine/CX3CR1 interactions following activation of innate immunity related to acute epipharyngitis may play a crucial role in glomerular vasculitis, resulting in worsening of hematuria.…”

Section: Role Of the Epipharyngeal Lymphoid Tissue In Iganmentioning

confidence: 99%

“…The accumulation of neutrophils in the glomeruli is essential in the development of Glomerular vasculitis in patients with IgAN [ 4 ]. Although the precise mechanism is unknown, we suspect that neutrophil accumulation mainly occurs locally and concomitantly with glomerular infiltration of CX3CR1+ cells [ 55 ].…”

Section: Role Of the Epipharyngeal Lymphoid Tissue In Iganmentioning

confidence: 99%

“…Circulating proinflammatory cytokines also enhance the expression of fractalkine and other adhesion molecules such as E- and P-selectins in glomerular endothelial cells. Upregulation of the fractalkine/CX3CR1 interaction and IL17 secreted by infiltrated glomerular CX3CR1+ leukocytes, which promotes the influx of neutrophils, leads to the development of Glomerular vasculitis and subsequent rupture of the glomerular capillary wall, which is clinically associated with worsening of hematuria [ 55 ].…”

Section: Figurementioning

confidence: 99%

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Role of Palatine Tonsil and Epipharyngeal Lymphoid Tissue in the Development of Glomerular Active Lesions (Glomerular vasculitis) in Immunoglobulin A Nephropathy

Hasegawa¹,

Ieiri²,

Nagai³

et al. 2022

IJMS

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Hematuria is an essential symptom of immunoglobulin A nephropathy (IgAN). Although the etiology of hematuria in IgAN has not been fully elucidated, it is thought that the rupture of the glomerular basement membranes caused by intra-capillary leukocyte influx, so-called glomerular vasculitis, is the pathological condition responsible for severe hematuria. Glomerular vasculitis are active lesions that exist in the glomeruli of acute phase IgAN and it is important because it is suspected to make the transition to segmental glomerular sclerosis (SGS) as a repair scar lesion in the chronic phase, and the progression of SGS would eventually lead to glomerular obsolescence. Worsening of hematuria concomitant with acute pharyngitis is common in patients with IgAN; therefore, elucidating the relationship between the immune system of Waldeyer’s ring, including the palatine tonsil and epipharyngeal lymphoid tissue, and the glomerular vasculitis may lead to understanding the nature of IgAN. The epipharynx is an immunologically activated site even under normal conditions, and enhanced activation of innate immunity is likely to occur in response to airborne infection. Hyperactivation of innate immunity via upregulation of Toll-like receptors in the interfollicular area of the palatine tonsil and epipharyngeal lymphoid tissue, followed by enhanced fractalkine/CX3CR1 interactions, appears to play an important role in the development of glomerular vasculitis in IgAN. As latent but significant epipharyngitis is present in most patients with IgAN, it is plausible that acute upper respiratory infection may contribute as a trigger for the innate epipharyngeal immune system, which is already upregulated in a chronically inflamed environment. Given that epipharyngitis and its effects on IgAN are not fully understood, we propose that the so-called “epipharynx–kidney axis” may provide an important focus for future research.

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Section: Role Of the Epipharyngeal Lymphoid Tissue In Iganmentioning

confidence: 99%

Section: Role Of the Epipharyngeal Lymphoid Tissue In Iganmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Role of Palatine Tonsil and Epipharyngeal Lymphoid Tissue in the Development of Glomerular Active Lesions (Glomerular vasculitis) in Immunoglobulin A Nephropathy

Hasegawa¹,

Ieiri²,

Nagai³

et al. 2022

IJMS

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“…Some patients experience synpharyngitic gross hematuria even after undergoing a tonsillectomy. Immune responses in nasopharynx-associated lymphoid tissue, particularly in the epipharynx, are suggested to play important roles in this condition, and the concept of the epipharynx-kidney axis has recently been proposed [ 35 ]. Indeed, in murine IgAN, nasal immunization with CpG-ODN was shown to exacerbate kidney injury, whereas that by oral gavage did not [ 36 ].…”

Section: Associations Among Infections Human Cd56 + T Cells and Cd56 + Nk Cells And Renal Diseasesmentioning

confidence: 99%

Infections, Reactions of Natural Killer T Cells and Natural Killer Cells, and Kidney Injury

Uchida

Seki

Oda

2022

IJMS

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Natural killer T (NKT) cells and NK cells are representative innate immune cells that perform antitumor and antimicrobial functions. The involvement of these cells in various renal diseases, including acute kidney injury (AKI), has recently become evident. Murine NKT cells are activated and cause AKI in response to various stimuli, such as their specific ligand, cytokines, and bacterial components. Both renal vascular endothelial cell injury (via the perforin-mediated pathway) and tubular epithelial cell injury (via the tumor necrosis factor-alpha/Fas ligand pathway) are independently involved in the pathogenesis of AKI. NK cells complement the functions of NKT cells, thereby contributing to the development of infection-associated AKI. Human CD56+ T cells, which are a functional counterpart of murine NKT cells, as well as a subpopulation of CD56+ NK cells, strongly damage intrinsic renal cells in vitro upon their activation, possibly through mechanisms similar to those in mice. These cells are also thought to be involved in the acute exacerbation of pre-existing glomerulonephritis triggered by infection in humans, and their roles in sepsis-associated AKI are currently under investigation. In this review, we will provide an overview of the recent advances in the understanding of the association among infections, NKT and NK cells, and kidney injury, which is much more profound than previously considered. The important role of liver macrophages in the activation of NKT cells will also be introduced.

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“…The epipharynx is a primary target for SARS-CoV-2 replication in the early stages of COVID-19 [ 9 ]. The activated lymphoid tissue of the epipharynx produces various inflammatory cytokines for the clearance of pathogens and this immune activation is considered to be one of the pathologies of ME/CFS [ 10 , 11 , 12 ]. A relationship has already been established between chronic epipharyngitis and ME/CFS, and epipharyngeal abrasive therapy (EAT), a treatment for chronic epipharyngitis in Japan, is reported to be effective against ME/CFS [ 9 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment

Imai

Yamano

Nishi

et al. 2022

Viruses

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COVID-19 often causes sequelae after initial recovery, referred to collectively as long COVID. Long COVID is considered to be caused by the persistence of chronic inflammation after acute COVID-19 infection. We found that all long COVID patients had residual inflammation in the epipharynx, an important site of coronavirus replication, and some long COVID symptoms are similar to those associated with chronic epipharyngitis. Epipharyngeal abrasive therapy (EAT) is a treatment for chronic epipharyngitis in Japan that involves applying zinc chloride as an anti-inflammatory agent to the epipharyngeal mucosa. In this study, we evaluated the efficacy of EAT for the treatment of long COVID. The subjects in this study were 58 patients with long COVID who were treated with EAT in the outpatient department once a week for one month (mean age = 38.4 ± 12.9 years). The intensities of fatigue, headache, and attention disorder, which are reported as frequent symptoms of long COVID, were assessed before and after EAT using the visual analog scale (VAS). EAT reduced inflammation in the epipharynx and significantly improved the intensity of fatigue, headache, and attention disorder, which may be related to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These results suggest that EAT has potential as a novel method for long COVID treatment.

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The epipharynx-kidney axis triggers glomerular vasculitis in immunoglobulin A nephropathy

Cited by 7 publications

References 56 publications

Role of Palatine Tonsil and Epipharyngeal Lymphoid Tissue in the Development of Glomerular Active Lesions (Glomerular vasculitis) in Immunoglobulin A Nephropathy

Role of Palatine Tonsil and Epipharyngeal Lymphoid Tissue in the Development of Glomerular Active Lesions (Glomerular vasculitis) in Immunoglobulin A Nephropathy

Infections, Reactions of Natural Killer T Cells and Natural Killer Cells, and Kidney Injury

Epipharyngeal Abrasive Therapy (EAT) Has Potential as a Novel Method for Long COVID Treatment

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