Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.

Project description:Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus infected cells and produce various cytokines1,2. We report here a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but express c-Kit, Sca-1, IL-7R and IL-33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue â??FALCâ?? for fat-associated lymphoid cluster. FALC Lin-c-Kit+Sca-1+ cells are distinct from lymphoid progenitors3 and lymphoid tissue inducer (LTi) cells4. These cells proliferate in response to IL-2 and produce large amounts of Th2 cytokines such as IL-5, IL-6 and IL-13. IL-5 and IL-6 regulate B cell antibody production and self-renewal of B1 cells5-7. Indeed, FALC Lin-c-Kit+Sca-1+ cells support the self-renewal of B1 cells and enhance IgA production. IL-5 and IL-13 mediate allergic inflammation and protection against helminth infection8,9. Upon helminth infection and in response to IL-33, FALC Lin-c-Kit+Sca-1+ cells produce large amounts of IL-13, which leads to goblet cell hyperplasia, a critical step for helminth expulsion. In mice devoid of FALC Lin-c-Kit+Sca-1+ cells such goblet cell hyperplasia was not induced. Thus, FALC Lin-c-Kit+Sca-1+ cells are Th2-type innate lymphocytes and we propose that these cells be called â??natural helper cellsâ??. Experiment Overall Design: Natural helper cells (Lin- c-kit+ Sca-1+) were isolated from mesentery of C57BL/6 for RNA extraction and hybridization on Affymetrix microarrays. For the control of this experiment, we use double negative cells (DN2) from thymus of C57BL/6 or lymphoid tissue inducer cells (LTi). Thymic DN2 cells were prepared from adult thymocytes. Thymocytes were stained with magnetic beads conjugated with anti-CD4 and anti-CD8Î± mAbs and CD4-CD8- double negative (DN) cells were negatively sorted by AutoMACS. DN cells were further stained with anti-CD25 and anti-CD44 mAbs and CD25+CD44+ cells were sorted as DN2 cells on a FACSAria.Thy-1+CD4- LTi cells were prepared from fetal liver cells as described previously. c-Kit+Î±4Î²7+IL-7RÎ±+ fetal liver cells from day 13 embryos were cultured on TSt4 cells for 17 days.

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Homo sapiens

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