Lambda interferons mediate antiviral immunity by inducing interferon-stimulated genes (ISGs) in epithelial tissues. A common variant rs368234815TT/∆G creating functional gene from an IFNL4 pseudogene is associated with the expression of major ISGs in the liver but impaired clearance of hepatitis C. To explain this, we compared Halo-tagged and non-tagged IFNL3 and IFNL4 signaling in liver-derived cell lines. Transfection with non-tagged IFNL3, non-tagged IFNL4 and Halo-tagged IFNL4 led to a similar degree of JAK-STAT activation and ISG induction; however, the response to transfection with Halo-tagged IFNL3 was lower and delayed. Transfection with non-tagged IFNL3 or IFNL4 induced no transcriptome change in the cells lacking either IL10R2 or IFNLR1 receptor subunits. Cytosolic overexpression of signal peptide-lacking IFNL3 or IFNL4 in wild type cells did not interfere with JAK-STAT signaling triggered by interferons in the medium. Finally, expression profile changes induced by transfection with non-tagged IFNL3 and IFNL4 were highly similar. These data do not support the hypothesis about IFNL4-specific non-canonical signaling and point out that functional studies conducted with tagged interferons should be interpreted with caution.
- MeSH
- buněčné linie MeSH
- buňky Hep G2 MeSH
- exprese genu MeSH
- genový knockout MeSH
- hepatocyty imunologie metabolismus MeSH
- interferonové regulační faktory genetika metabolismus MeSH
- interferony nedostatek genetika metabolismus MeSH
- interleukiny nedostatek genetika metabolismus MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- receptor interleukinu-10 - beta-podjednotka nedostatek genetika metabolismus MeSH
- receptory interferonů nedostatek genetika metabolismus MeSH
- rekombinantní proteiny genetika metabolismus MeSH
- signální transdukce MeSH
- transfekce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Wound healing and tissue regeneration is an intricate biological process that involves repair of cellular damage and maintenance of tissue integrity. Cascades involved in wound healing and tissue regeneration highly overlap with cancer causing pathways. Usually, subsequent tissue damage events include release of a number of cytokines to accomplish post-trauma restoration. IL-22 is one of the cytokines that are immediately produced to initiate immune response against several tissue impairments. IL-22 is a fundamental mediator in inflammation, mucous production, protective role against pathogens, wound healing, and tissue regeneration. However, accumulating evidence suggests pivotal role of IL-22 in instigation of various cancers due to its pro-inflammatory and tissue repairing activity. In this review, we summarize how healing effects of IL-22, when executed in an uncontrollable fashion can lead to carcinogenesis.
- MeSH
- hlen metabolismus MeSH
- hojení ran fyziologie MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- infekce imunologie metabolismus MeSH
- interleukiny škodlivé účinky antagonisté a inhibitory nedostatek fyziologie MeSH
- karcinogeneze MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- myši MeSH
- nádory etiologie patofyziologie MeSH
- neutralizující protilátky terapeutické užití MeSH
- přirozená imunita fyziologie MeSH
- psoriáza farmakoterapie imunologie MeSH
- receptory interleukinů fyziologie MeSH
- regenerace fyziologie MeSH
- revmatoidní artritida farmakoterapie imunologie MeSH
- T-lymfocyty - podskupiny imunologie metabolismus MeSH
- zánět patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Celulárnu adaptívnu imunitnú odpověď zabezpečujú T-lymfocyty. Tieto sú vo svojej funkcii róznorodé, čo nemóže zabezpečit'jedna skupina buniek, ale len viaceré. Vskutku, na základe odlišných biologických vlastností sa T-lymfocyty delia na tri základné subpopulácie - pomocné, cytotoxické a regulačně. Navýše pomocné T-lymfocyty možno rozdělit' na ďalšie subpopulácie, ktorých v súčasnosti poznáme už 6: THl, TH2, TH5,TH9,TH17 a TH22. TH2-lymfocyty sú principiálnymi buňkami, ktoré zabezpečujú obranyschopnost' proti helmintom. Vznikajú však pomerne neskoro, takže sa hľadali iné bunky, ktoré by produkciou rovnakých cytokínov ako syntetizujú TH 2-lymfocyty túto odpoveď iniciovali okamžite po infestácii parazitmi. Ich objavu predchádzalo objavenie IL-25 a IL-33, ktoré sú podstatnými cytokínmi indukujúcimi vznik týchto buniek, ktoré dostali pomenovanie „prirodzené imunitné bunky“. Zahrň ujú 4 rozdielne, ale príbuzné populácie buniek s názvami: nuocyty, bunky NH, MPP type2 a Ih2. Okrem fyziologickej úlohy boja proti helmintom, podpory vzniku TH2 adaptívnej imunity, možného blokovania zápalu v tukovom tkanive a diferenciácie na bazofily a mastocyty sa zúčastň ujú aj na imunopatologických procesoch – rozvoji alergie a zápalových chorôb čreva. K uvedeným prirodzeným bunkám možno ešte priradiť MAIT- a ILC22-bunky. Zabezpečujú antiinfekčnú ochranu a homeostázu tkanív.
Cellular adaptive immune response is mediated by T cells. Their biological activities are very heterogeneous what precludes to be mediated by a single cell population, rather by several ones. Really, T cells can be divided into three basic subpopulations – helper, cyto toxic and regulato- ry. Moreover, within T helper cell population six distinctive subsets can be distinguished - T H 1, T H 2, T H 5, T H 9, T H 17, and T H 22, respectively. T H 2 lymphocytes are principal cells responsible for fighting helminths. They appear, however, relatively late during the immune r esponse what made researchers to look for other cells endowed of T H 2 cytokines synthesis immediately after parasites infestation. Their discovery was successful because of previous description of new cytokines – IL-25 and IL-33, respectively, which are necessary for the induct ion of these novel innate immune cell populations (IICs). They comprise 4 different populations: nuocytes, NH2, MPP type2 and Ih2 cells, respectively. Their principal physiological role is not only to fight helminths, however, they support the induction of T H 2 adaptive immune response, down-regulate inflammation in a fat tissue and some of them differentiate into mast cells and basophils. ICCs can take part in immunopatholog ical processes too, esp. in allergy and IBD development. One can include to the innate cell population also other innate cells, namely MAIT an d ILC22, re- spectively. They are involved in anti-infectious immunity and tissue homeostasis.
