IL-9 has been shown to be upregulated before the clinical onset of articular disease in RA. The exact role of IL-9 and Th9 cells in RA, however, has not yet been adequately studied. The aim of this ...study was to evaluate the expression of IL-9 and IL-9-expressing cells in RA patients.
IL-9, IL-9R, PU.1, IL-9, thymic stromal lymphopoietin (TSLP), IL-4 and TGF-β expression was assessed by real-time-PCR in the synovial tissues of RA and OA patients. IL-9, IL-9R, IL-4, TSLP and TGF-β were also investigated by immunohistochemistry. Peripheral CD4(+) T cell subsets were studied by flow cytometry analysis before and after incubation with citrullinated peptides.
IL-9 was overexpressed in RA synovial tissues and correlated with the degree of histological organization of B and T cells in ectopic lymphoid structures. The majority of IL-9-producing cells were identified as CD3(+) cells. Increased mRNA and protein expression of IL-9R, IL-4, TSLP and TGF-β was also observed in RA synovial tissue. Blood peripheral Th9 cells were expanded by citrullinated peptides.
These results indicate that Th9 cells and IL-9 were frequently detected in peripheral blood mononuclear cells and synovia of RA patients. A possible pathogenic role for Th9 in RA is discussed.
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.
Educational tests are standardized so that all examinees are tested on the same material, under the same testing conditions, and with the same scoring protocols. This uniformity is designed to ...provide a level “playing field” for all examinees so that the test is “the same” for everyone. Thus, standardization is designed to promote fairness in testing. In practice, the material tested, the conditions under which a test is administered, and the scoring processes, are often too rigid to provide the intended level playing field. For example, standardized testing conditions may interact with personal characteristics of examinees that affect test performance, but are not construct‐relevant. Thus, more flexibility in standardization is needed to account for the diversity of experiences, talents, and handicaps of the incredibly heterogeneous populations of examinees we currently assess. Traditional standardization procedures grew out of experimental psychology and psychophysics laboratories where keeping all conditions constant was crucial. Today, accounting for and measuring what is not constant across examinees is crucial to valid construct interpretations. To meet this need I introduce the concept of understandardization, which refers to ensuring sufficient flexibility in standardized testing conditions to yield the most accurate measurement of proficiency for each examinee.
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 Trends in International Mathematics and Science Study (TIMSS) makes it possible to compare the performance of students in the US in Mathematics and Science to the performance of students in other ...countries. TIMSS uses four international benchmarks for describing student achievement: Low, Intermediate, High, and Advanced. In this study, we linked the eighth-grade Math TIMSS and NAEP scales using equipercentile equating to (a) help better interpret U.S. eighth-grade students’ performance on TIMSS, and (b) investigate the progress of eighth-grade U.S. students over time relative to the progress of students in other countries. Results indicated that relative to other countries, U.S. eighth-grade students increased with respect to the “At or Above Basic” NAEP Achievement level, but that other countries saw larger improvements in the higher achievement level categories, relative to the US. This finding may reflect the emphasis of No Child Left Behind on raising lower achievement to “proficient.” However, with respect to “Advanced” mathematics achievement, eighth-grade U.S. students showed less improvement than students in other countries.
Summary
The aim of this study was to elucidate more clearly the role of interleukin (IL)‐18 in modulating the IL‐22 pathway in primary Sjögren's syndrome (pSS) patients and in pSS‐associated ...lymphomas. Minor salivary glands (MSGs) from patients with pSS and non‐specific chronic sialoadenitis (nSCS), parotid glands biopsies from non‐Hodgkin lymphomas (NHL) developed in pSS patients, were evaluated for IL‐18, IL‐22, IL‐22 receptor 1 (IL‐22R1), IL‐22 binding protein (IL‐22BP) and signal transducer and activator of transcription‐3 (STAT‐3) expression. MSGs IL‐22R1‐expressing cells were characterized by confocal microscopy and flow cytometry in pSS, nSCS and healthy controls . The effect of recombinant IL‐18 and IL‐22 on peripheral blood mononuclear cells (PBMCs) from pSS and nSCS was studied by flow cytometry and reverse transcription–polymerase chain reaction (RT‐PCR). MSGs of pSS and NHL were characterized by an imbalance between IL‐22 and IL‐22BP protein expression, with IL‐18 and IL‐22BP being expressed in a mutually exclusive manner and IL‐18 and IL‐22R1 being correlated directly. Aberrant expression of IL‐22R1, induced by IL‐18, was observed only among tissue and circulating myeloid cells of pSS patients and macrophages of NHL tissues of pSS patients, but not nSCS. IL‐22R1 expression on PBMC of pSS was functional, as its stimulation with recombinant IL‐22 significantly up‐regulated the expression of STAT‐3, IL‐17 and IL‐22. An IL‐18‐dependent aberrant expression of IL‐22R1 on cells of haematopoietic origin seems to be a specific immunological signature of patients with pSS and pSS‐associated lymphomas.
Many behavioral scientists argue that assessments used in social indicators research must be content-valid. However, the concept of content validity has been controversial since its inception. The ...current unitary conceptualization of validity argues against use of the term content validity, but stresses the importance of content representation in the instrument construction and evaluation processes. However, by arguing against use of this term, the importance of demonstrating content representativeness has been severely undermined. This paper reviews the history of content validity theory to underscore its importance in evaluating construct validity. It is concluded that although measures cannot be "validated" based on content validity evidence alone, demonstration of content validity is a fundamental requirement of all assessment instruments.
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