Cytokines such as tumour necrosis factor (TNF)- alpha , interleukin (IL)-12, interferon (IFN)- gamma , IL-23 and, more recently, IL-9, have been implicated in the initiation/maintenance of ...inflammation in psoriasis and psoriatic arthritis (PsA). In the present study we aimed to characterize the role of gamma delta T cells in peripheral blood and synovial fluid of PsA patients and to investigate their response to in-vitro stimulation with antigen or cytokines (IL-9 and IL-23). gamma delta T cells isolated from peripheral blood mononuclear cells and synovial fluid were analysed by flow cytometry to evaluate the phenotype and cytokine production. IL-23R and IL-9R gene expression were also evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Peripheral blood mononuclear cells (PBMC), sorted gamma delta T cells and gamma delta cell lines were also stimulated in vitro with isopentenyl pyrophosphate (IPP), recombinant IL-9 or recombinant IL-23. Our results show an expansion of gamma delta T cells with a predominant effector memory phenotype in peripheral blood and synovium of untreated PsA patients, which reverses significantly after treatment with anti-TNF- alpha or anti-IL-12/IL-23R monoclonal antibodies (mAbs). Moreover, in PsA patients gamma delta T cells activation is driven prevalently by IL-9/IL-9R interaction, and not only by IL-23/IL-23R. Together these findings indicate gamma delta T cells and IL-9 as new players in the pathogenesis of PsA. IL-9/IL-9R axis drives gamma delta T cells activation in psoriatic arthritis patients
Summary
T helper 9 (Th9) cells and interleukin (IL)‐9 are involved in the pathogenesis of several autoimmune diseases. The exact role of IL‐9 and Th9 cells in patients with systemic sclerosis (SSc) ...have not yet been studied adequately. IL‐9, IL‐9R, transcription factor PU.1 (PU.1), IL‐4, thymic stromal lymphopoietin (TSLP) and transforming growth factor (TGF)‐β expression were assessed in skin and kidney biopsies of SSc patients and healthy controls (HC) by immunohistochemistry (IHC). The cellular source of IL‐9 was also analysed by confocal microscopy analysis. Peripheral IL‐9‐producing cells were also studied by flow cytometry. The functional relevance of IL‐9 increased expression in SSc was also investigated. Our results demonstrated a strong expression of IL‐9, IL‐9R, IL‐4, TSLP and TGF‐β in skin tissues of patients with both limited and diffuse SSc. IL‐9 expression was observed mainly in the context of skin infiltrating mononuclear cells and keratinizing squamous epithelium. IL‐9 over‐expression was also observed in renal biopsies of patients with SSc. IL‐9 producing cells in the skin were identified as Th9 cells. Similarly, Th9 cells were expanded and were the major source of IL‐9 among SSc peripheral blood mononuclear cells (PBMC), their percentage being correlated directly with the modified Rodnan skin score. Infiltrating mononuclear cells, mast cells and neutrophils expressed IL‐9R. In in‐vitro studies stimulation with rIL‐9 significantly induced NET (neutrophil extracellular traps) release by dying cells (NETosis) in neutrophils, expansion of mast cells and increase of anti‐systemic scleroderma 70 (Scl70) production by B cells. Our findings suggest that Th9 cells and IL‐9 could be implicated in the pathogenesis of SSc.
IL‐9 and Th9 cells are expanded in the skin, kidney and peripheral blood of SSc patients.
IL‐9 pathway may play an important role in SSc and should be considered as potential therapeutic target in SSc.
Summary
Cytokines such as tumour necrosis factor (TNF)‐α, interleukin (IL)‐12, interferon (IFN)‐γ, IL‐23 and, more recently, IL‐9, have been implicated in the initiation/maintenance of inflammation ...in psoriasis and psoriatic arthritis (PsA). In the present study we aimed to characterize the role of γδ T cells in peripheral blood and synovial fluid of PsA patients and to investigate their response to in‐vitro stimulation with antigen or cytokines (IL‐9 and IL‐23). γδ T cells isolated from peripheral blood mononuclear cells and synovial fluid were analysed by flow cytometry to evaluate the phenotype and cytokine production. IL‐23R and IL‐9R gene expression were also evaluated by reverse transcription–polymerase chain reaction (RT–PCR). Peripheral blood mononuclear cells (PBMC), sorted γδ T cells and γδ cell lines were also stimulated in vitro with isopentenyl pyrophosphate (IPP), recombinant IL‐9 or recombinant IL‐23. Our results show an expansion of γδ T cells with a predominant effector memory phenotype in peripheral blood and synovium of untreated PsA patients, which reverses significantly after treatment with anti‐TNF‐α or anti‐IL‐12/IL‐23R monoclonal antibodies (mAbs). Moreover, in PsA patients γδ T cells activation is driven prevalently by IL‐9/IL‐9R interaction, and not only by IL‐23/IL‐23R. Together these findings indicate γδ T cells and IL‐9 as new players in the pathogenesis of PsA.
IL‐9/IL‐9R axis drives gamma delta T cells activation in psoriatic arthritis patients
The objective of the paper is to evaluate the potential of tank-based rainwater harvesting systems as source control methods to mitigate runoff flow peaks in urban areas. Water balance simulations of ...the rainwater tanks at the resolution time scale of 1minute were carried out for this purpose using both high-resolution rainfall series and toilet water demand data from a previous experimental campaign, which involved six experimental households in southern Italy. Simulations show that significant reduction of the flow peak may be obtained with rainwater tanks depending on the tank size and on the household water demand.
Summary Granulysin is a recently identified cytolytic protein which is expressed by human cytotoxic T-lymphocytes and natural killer (NK)-cells, and has broad antimicrobial and tumoricidal activity. ...Circulating granulysin levels are associated with T- and NK-cell activity, and may thus reflect protection-associated cellular immune responses. In a case-control study in Indonesia, a highly tuberculosis (TB)-endemic country, we therefore determined plasma granulysin levels in adults with active pulmonary TB before, during, and after TB treatment, both in mild/moderate-TB and advanced-TB patients, and compared these to healthy neighbourhood controls. Adults with active pulmonary TB had significantly lower plasma granulysin levels compared to controls. After 2 months of anti-TB therapy, levels in TB patients had significantly increased, reaching values similar to those in controls. Plasma granulysin levels further increased after completion of TB therapy, being significantly higher than those in controls. Plasma granulysin levels correlated inversely with TB disease activity but not with TB disease severity. In contrast, plasma interferon- γ (IFN- γ ) levels were significantly higher in active TB cases than in controls, normalised during treatment and correlated with both TB disease activity and TB disease severity. At the cellular level, granulysin and IFN- γ expression both correlated inversely with disease activity. Interestingly, granulysin was predominantly expressed by IFN- γ negative T-cells, suggesting that the cellular sources of IFN- γ and granulysin in TB are partly non-overlapping. The observation that plasma granulysin levels and cellular IFN- γ production correlate with curative host responses in pulmonary tuberculosis points to a potentially important role of granulysin, next to IFN- γ , in host defence against M. tuberculosis.
Interleukin 9 (IL-9) is a mediator of tissue damage in several inflammatory diseases. In this study we aimed to evaluate the effects of in vivo IL-9 neutralisation in mice developing collagen induced ...arthritis (CIA).
DBA/1 were immunised with collagen in Freund's complete adjuvant (CFA) to induce arthritis. Anti-IL-9 mAb was injected in mice after the onset of arthritis (Group A) or on the same day as sensitisation and again on the day of the challenge (Group B). Histological analysis was performed in joints of mice and spleen cells were also analysed by flow cytometry. A geneset analysis was carried out on whole tarsal joint tissue transcriptomes.
IL-9 was over-expressed in swollen joints of mice developing arthritis. Treatment with anti-IL-9 mAb after arthritis onset efficiently down-modulated the severity of joint inflammation. Similarly, anti-IL-9 mAb administered on the same day as sensitisation and on the day of challenge also delayed the onset of arthritis. Anti-IL-9 mAb injection after the onset of arthritis was associated with a decrease of CD4+ TNF-α+ cells and an increase of CD4+ FoxP3+ IL-10+ cells. Geneset analysis in CIA showed an up-regulation of GATA3 with no significant direct interactions between IL-9 and GATA3, which instead was mediated by IL-5 through STAT6.
Our results suggest that IL-9 is involved in the immunopathogenesis of CIA. Further implications for the clinical translation of our findings are discussed.
Oral pathology in untreated coelic disease CAMPISI, G.; DI LIBERTO, C.; IACONO, G. ...
Alimentary pharmacology & therapeutics,
December 2007, Letnik:
26, Številka:
11‐12
Journal Article
Recenzirano
Odprti dostop
Summary
Background Many coeliac disease patients with atypical symptoms remain undiagnosed.
Aim To examine the frequency of oral lesions in coeliac disease patients and to assess their usefulness ...in making coeliac disease diagnosis.
Patients and methods One hundred and ninety‐seven coeliac disease patients and 413 controls were recruited and the oral examination was performed.
Results Forty‐six out of 197 coeliac disease patients (23%) were found to have enamel defects vs. 9% in controls (P < 0.0001). Clinical delayed eruption was observed in 26% of the pediatric coeliac disease patients vs. 7% of the controls (P < 0.0001). The prevalence of oral soft tissues lesions was 42% in the coeliac disease patients and 2% in controls (P < 0.0001). Recurrent aphthous stomatitis disappeared in 89% of the patients after 1 year of gluten‐free diet. Multi‐logistic analysis selected the following variables as the most meaningful in coeliac disease patients: dental enamel defects (OR = 2.652 CI = 1.427–4.926) and soft tissue lesions (OR = 41.667, CI = 18.868–90.909). Artificial Neural Networks methodology showed that oral soft tissue lesions have sensitivity = 42%, specificity = 98% and test accuracy = 83% in coeliac disease diagnosis.
Conclusions The overall prevalence of oral soft tissue lesions was higher in coeliac disease patients (42%) than in controls. However, the positive‐predictive value of these lesions for coeliac disease diagnosis was low.
PDF
