Activation of interleukin 33-NFκB axis in granulosa cells during atresia and its role in disposal of atretic follicles†.

It has been previously shown that the cytokine interleukin 33 is required for two processes, i.e., autophagic digestion of granulosa cells and recruitment of macrophages into atretic follicles, for full disposal of atretic follicles.

Role of Interleukin33 in Rejuvenation of Aged Neurons and Age-Related Dementias.

Late-onset Alzheimer's disease (LOAD) is the most common age-related dementia, and its etiology remains unclear. Recent studies have linked abnormal neuronal aging to LOAD. Neurons are non-proliferative, and thus, majority of aged neurons must be rejuvenated through repairing or eliminating damaged molecules to regain their healthy status and functionalities.

Requirement of brain interleukin33 for aquaporin4 expression in astrocytes and glymphatic drainage of abnormal tau.

Defective aquaporin4 (AQP4)-mediated glymphatic drainage has been linked to tauopathy and amyloid plaque in Alzheimer's disease. We now show that brain interleukin33 (IL33) is required for regulation of AQP4 expression in astrocytes, especially those at neuron-facing membrane domain (n-AQP4). First, IL33-deficient (Il33) mice showed a loss of n-AQP4 after middle age, which coincided with a rapid accumulation of abnormal tau in neurons and a reduction in drainage of abnormal tau to peripheral tissues.

Inter-molecular epitope spreading does not lead to extension of autoimmunity beyond target tissue in autoimmune glomerulonephritis.

Inter-molecular epitope spreading during autoimmune pathogenesis leads to generation of new pathogenic epitopes on other autoantigens beyond the original one. It raises an important question as whether autoimmunity extends beyond the target tissues if new epitopes are on the molecules shared with other tissues. This study is aimed addressing this question in a rat anti-glomerular basement membrane (GBM) glomerulonephritis model induced by a T cell epitope of glomerulus-specific collagen4α3.

Glymphatic Efficiency Is a Critical Factor for Using Abnormal Tau in Peripheral Tissues as Biomarker for Alzheimer's Disease.

Alzheimer's Disease or other dementias are characterized by the accumulation of abnormal tau and amyloid β peptides in brains. Therefore, abnormal tau and amyloid peptides in peripheral tissues or blood have been explored as diagnostic biomarkers. On the other hand, recent studies have revealed glymphatics a special drainage system for brain's wastes.

CD8αα+MHC Class II+ Cell with the Capacity To Terminate Autoimmune Inflammation Is a Novel Antigen-Presenting NK-like Cell in Rats.

Discovery of immune tolerance mechanisms, which inhibit pre-existing autoimmune inflammation, may provide us with new strategies for treating autoimmune diseases. We have identified a CD8ααMHC class II cell with professional APC capacity during our investigation on spontaneous recovery from autoimmune glomerulonephritis in a rat model. This cell actively invades inflamed target tissue and further terminates an ongoing autoimmune inflammation by selective killing of effector autoreactive T cells.

Differentiating Glomerular Inflammation from Fibrosis in a Bone Marrow Chimera for Rat Anti-Glomerular Basement Membrane Glomerulonephritis.

Background: Many types of glomerulonephritis (GN) undergo tandem connected phases: inflammation and fibrosis. Fibrosis in human GNs leads to irreversible end-stage disease. This study investigated how these 2 phases were controlled.

IL-33 is required for disposal of unnecessary cells during ovarian atresia through regulation of autophagy and macrophage migration.

Physiological processes such as ovarian follicle atresia generate large amounts of unnecessary cells or tissue detritus, which needs to be disposed of rapidly. IL-33 is a member of the IL-1 cytokine gene family. Constitutive expression of IL-33 in a wide range of tissues has hinted at its role beyond immune defense.

Unique temporal and spatial expression patterns of IL-33 in ovaries during ovulation and estrous cycle are associated with ovarian tissue homeostasis.

Ovaries are among the most active organs. Frequently occurring events such as ovulation and ovarian atresia are accompanied with tissue destruction and repairing. Critical roles of immune cells or molecules in those events have been well recognized.

Peripheral blood CD8αα+CD11c+MHC-II+CD3- cells attenuate autoimmune glomerulonephritis in rats.

In an anti-glomerular basement membrane (GBM) glomerulonephritis (GN) model, GN-resistant Lewis rats naturally recover from early glomerular inflammation. Here we investigated recovery mechanisms for development of a potential immunotherapy for autoimmune GN. Our previous studies suggested that glomeruli-infiltrating leukocytes with a phenotype of CD8αα+CD11c+MHC-II+CD3- (GIL CD8αα+ cells) were responsible for recovery through induction of T-cell apoptosis.

Ovarian phagocyte subsets and their distinct tissue distribution patterns.

Ovarian macrophages, which play critical roles in various ovarian events, are probably derived from multiple lineages. Thus, a systemic classification of their subsets is a necessary first step for determination of their functions. Utilizing antibodies to five phagocyte markers, i.

Natural recovery from antiglomerular basement membrane glomerulonephritis is associated with glomeruli-infiltrating CD8α+CD11c+MHC class II+ cells.

Background/aims: In an antiglomerular basement membrane glomerulonephritis (GN) model, GN-resistant Lewis (LEW) rats naturally recover from early glomerular inflammation (days 21-23). We have previously identified a glomeruli-infiltrating CD8α(+)CD11(high)MHC II(+) cell (GIL CD8α(+) cell) in GN-prone Wistar Kyoto (WKY) rats, which terminates glomerular inflammation through inducing T cell apoptosis prior to glomerular fibrosis at days 35-40. We investigated if GIL CD8α(+) cells were also associated with the recovery in LEW rats.

Blockade of osteopontin inhibits glomerular fibrosis in a model of anti-glomerular basement membrane glomerulonephritis.

Background: In our rat model for anti-GBM GN, severe fibrosis follows glomerular inflammation. A potential role of extracellular matrix protein osteopontin (OPN) in glomerular fibrosis was investigated.

Methods: Neutralizing OPN antiserum or control normal serum was injected into the experimental rats at late inflammatory/early fibrotic stage.

Osteopontin overproduction is associated with progression of glomerular fibrosis in a rat model of anti-glomerular basement membrane glomerulonephritis.

Background: Glomerular fibrosis is the common end result of glomerulonephritis (GN) regardless of etiology. In our rat model for anti-glomerular basement membrane GN, severe fibrosis follows glomerular inflammation. We investigated the association between expression of extracellular matrix (ECM) proteins and progression of glomerular fibrosis.

Identification of a bone marrow-derived CD8αα+ dendritic cell-like population in inflamed autoimmune target tissue with capability of inducing T cell apoptosis.

DCs play critical roles in promotion of autoimmunity or immune tolerance as potent APCs. In our anti-GBM GN model, WKY rats develop severe T cell-mediated glomerular inflammation followed by fibrosis. A DC-like cell population (CD8αα(+)CD11c(+)MHC-II(+)ED1(-)) was identified in the inflamed glomeruli.

Anti-inflammatory and renal protective actions of stanniocalcin-1 in a model of anti-glomerular basement membrane glomerulonephritis.

We have previously shown that stanniocalcin-1 (STC1) inhibits the transendothelial migration of macrophages and T cells, suppresses superoxide generation in macrophages, and attenuates macrophage responses to chemoattractants. To study the effects of STC1 on inflammation, in this study we induced a macrophage- and T-cell-mediated model of anti-glomerular basement membrane disease in STC1 transgenic mice, which display elevated serum STC1 levels and preferentially express STC1 in both endothelial cells and macrophages. We examined the following parameters both at baseline and after anti-glomerular basement membrane antibody treatment: blood pressure; C(3a) levels; urine output; proteinuria; blood urea nitrogen; and kidney C(3) deposition, fibrosis, histological changes, cytokine expression, and number of T cells and macrophages.

Potential roles of a special CD8 alpha alpha+ cell population and CC chemokine thymus-expressed chemokine in ovulation related inflammation.

It is well known that ovulation may be an inflammatory process. However, it remains elusive how immune cells participate in this process. We have identified a novel CD8alpha alpha(+) population, which resembles tissue dendritic cells, in the theca of antral follicles.

Antibodies to two ZP3 B cell epitopes affect zona pellucida assembly.

Mouse zona pellucida (ZP) proteins are synthesized in developing oocytes and assembled into ZP after their secretion. This study has investigated whether anti-ZP3 antibodies affect ZP assembly. Peptides CP2 and CP3 were used to elicit antibodies to two ZP3 B cell epitopes, ZP3 (335-342) and ZP3 (171-180).

Spontaneous recovery from early glomerular inflammation is associated with resistance to anti-GBM glomerulonephritis: tolerance and autoimmune tissue injury.

Different susceptibility to anti-GBM glomerulonephritis (GN) among animal strains has been reported. Using our rat model for T cell-mediated anti-GBM GN, this study initiated an investigation on the mechanism related with GN susceptibility. Anti-GBM GN was induced either through immunization with the nephritogenic T cell epitope pCol(28-40) from Col4alpha3NC1 or through the transfer of specific T cells.

Repression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not its receptors during oral cancer progression.

Background: TRAIL plays an important role in host immunosurveillance against tumor progression, as it induces apoptosis of tumor cells but not normal cells, and thus has great therapeutic potential for cancer treatment. TRAIL binds to two cell-death-inducing (DR4 and DR5) and two decoy (DcR1, and DcR2) receptors. Here, we compare the expression levels of TRAIL and its receptors in normal oral mucosa (NOM), oral premalignancies (OPM), and primary and metastatic oral squamous cell carcinomas (OSCC) in order to characterize the changes in their expression patterns during OSCC initiation and progression.

Coincident activation of Th2 T cells with onset of the disease and differential expression of GRO-gamma in peripheral blood leukocytes in minimal change disease.

Background: Involvement of Th2 T cells/NFkappaB in minimal change disease (MCD) has been postulated. A promising but unconfirmed glomerular permeability factor (GPF) from MCD T cells has been described. We explored whether GPF was the consequence of Th2 cell activation.

T cell epitope mimicry in antiglomerular basement membrane disease.

Antiglomerular basement membrane (GBM) disease or Goodpasture's syndrome is among the earliest recognized human autoimmune diseases. Although collagen 4alpha3 NC1 (Col4alpha3NC1) has been identified as the responsible autoantigen, it remains unknown how autoimmunity to this autoantigen is provoked. We have demonstrated in our rat model that a single nephritogenic T cell epitope pCol28-40 of Col4alpha3NC1 induces glomerulonephritis.

Activation of glomerular basement membrane-specific B cells in the renal draining lymph node after T cell-mediated glomerular injury.

Linear binding of IgG to the glomerular basement membrane (GBM) is the hallmark of anti-GBM glomerulonephritis (GN). However, the precise mechanism by which diverse autoantibodies to GBM are induced in GN has not been determined. It was demonstrated previously that a single T cell epitope pCol(28-40) derived from collagen IV alpha3 chain not only induced severe GN in Wistar Kyoto rats but also triggered a diversified anti-GBM antibody response through "B cell epitope spreading.

Characterization of the T-cell epitope that causes anti-GBM glomerulonephritis.

Background: We have demonstrated that a single T-cell epitope pCol(28-40) (SQTTANPSCPEGT) alone, which is derived from NC1 domain of alpha3 chain of type IV collagen (Col4alpha3 NC1), can induce severe glomerulonephritis in Wistar Kyoto rats. This study further characterized this T-cell epitope.

Methods: A series of synthetic peptides derived from pCol (28-40) were tested in vivo and in vitro for their T-cell epitope activity and nephritogenicity.