Thus, in the first stage of their method dilutions of the FVIII containing sample were incubated with a source of FIXa, FX,

phospholipid and Ca2+ ions, in the absence of prothrombin. Subsamples were then taken and added to a source of prothrombin and fibrinogen (usually normal plasma), and clotting times were measured after addition of Ca2+ ions. In the original method, published in 1955 [8], platelets were used as the source of phospholipid, Nivolumab but as with the one-stage method this was soon replaced by a stable freeze-dried phospholipid reagent. Other technical variations were introduced over time, and these are reviewed elsewhere [9]. Detailed comparisons of the one-stage and two-stage methods have selleck screening library been published elsewhere [10]. Briefly, the one-stage method is simpler and easier to automate, but has a large variety of reagents (FVIII-deficient plasma and APTT reagents), which perhaps accounts for the fact that it is less precise. The two-stage method has less variation in reagents, which may explain why it is generally more precise, but is technically more complex and more difficult to automate. The latter problem has been circumvented by the introduction of chromogenic

substrates to measure the FXa produced in the first stage, and the chromogenic version has now largely replaced the original clotting method. Unlike the one-stage assay, the two-stage method does not 上海皓元医药股份有限公司 require a source of FVIII-deficient

plasma, a distinct advantage to control laboratories such as NIBSC and to manufacturers of concentrates. The one-stage assay remains the most popular in clinical laboratories, but the chromogenic method is used extensively by manufacturers and control laboratories, and is the official method of the European Pharmacopoeia (EP). When I joined NIBSC in 1974 my remit was to establish a laboratory for testing clotting factor concentrates and other coagulation-related products such as heparin, as well as to organize the development of national and international standards for these products. Initially, I worked in the Division of Hormones and Blood Products under Dr Derek Bangham, but a few years later Blood Products became a separate Division with Dr Duncan Thomas as Head. The procedure for establishment of international standards had been in place for many years under Dr Bangham as Head of the Biological Standards Division at the National Institute of Medical Research (NIMR), Mill Hill, before NIBSC was formed in the early 1970s. In fact this procedure started as far back as the 1920s when the NIMR was first formed – curiously enough this was initially in the same building at Hampstead where NIBSC was established, so it could be said that the Standards work eventually came back home.

Sixteen aggressive pathotypes were identified on the basis of percent coefficient of infection (PCI). Two major clusters were apparent in the dendrogram; cluster 1 comprised 13 isolates and cluster two consisted of seven isolates. One of the isolate Kashipur had a high PCI on most of the host differentials

compared to other isolates. Polymerase chain reaction-based random amplified polymorphic DNA (PCR – RAPD) analysis also divided isolates into two major clusters, one comprising of 5 isolates collected from hill and foot-hill sites GPCR Compound Library screening and another group comprising of 15 isolates collected from plain sites. Thus, the clusters identified based on PCI did not match closely with those identified by molecular analysis based on RAPD. Although diversity among the isolates of T. indica was absent in the rDNA-ITS region, our study based on pathogenicity and molecular markers confirms the existence of great diversity in the pathogen, also buy LBH589 shifting of ‘hot spot’ areas from one place to another within Karnal bunt prevailing areas. “
“The aim of this study was to observe the lipid peroxidation (LP) of cell membranes and antioxidant systems in response to inoculation

of Peronospora arborescens causing downy mildew (DM) in opium poppy. Contents of the LP product, malondialdehyde (MDA) and antioxidant glutathione (GSH) were determined in leaves of two opium poppy genotypes, Pps-1 (highly resistant to DM) and Jawahar-16 (highly susceptible to DM) at different time intervals after inoculation (12 h, 24 h, 48 h and 72 h). The provided GSH content corresponded to that of total non-protein sulfhydryl groups. In leaves of Jawahar-16, a significant decrease in concentration of GSH and a persistent increase in concentration of MDA were recorded after inoculation in comparison to leaves of control plants. The continuous decrease

in GSH content contributed to damage of cell membranes leading to disease development in Jawahar-16. On the other hand in a resistant genotype (Pps-1), initially at 12 h after inoculation (hai) the level of GSH was found to be high, but a transient and highly significant decrease in content of GSH and increase in content of MDA was observed at 24 hai in comparison to control plants of same genotype and also in comparison to inoculated plants of susceptible genotype (Jawahar-16). These results indicate that generation medchemexpress of GSH and MDA is negatively correlated during the infection process as found in the case of DM-resistant genotype Pps-1 at 24hai, which also suggests an increased need by the host plant for oxidative stress, required for hypersensitive response mediated defense mechanism. “
“Southern rice black-streaked dwarf virus (SRBSDV) causes southern rice black-streaked dwarf and maize rough dwarf diseases, which lead to severe yield losses of crops in Southeast Asia. We report here a SYBR Green I-based One-Step Real Time RT-PCR assay for quantifying SRBSDV in rice rapidly and accurately.

Sixteen aggressive pathotypes were identified on the basis of percent coefficient of infection (PCI). Two major clusters were apparent in the dendrogram; cluster 1 comprised 13 isolates and cluster two consisted of seven isolates. One of the isolate Kashipur had a high PCI on most of the host differentials

compared to other isolates. Polymerase chain reaction-based random amplified polymorphic DNA (PCR – RAPD) analysis also divided isolates into two major clusters, one comprising of 5 isolates collected from hill and foot-hill sites Tanespimycin supplier and another group comprising of 15 isolates collected from plain sites. Thus, the clusters identified based on PCI did not match closely with those identified by molecular analysis based on RAPD. Although diversity among the isolates of T. indica was absent in the rDNA-ITS region, our study based on pathogenicity and molecular markers confirms the existence of great diversity in the pathogen, also LBH589 shifting of ‘hot spot’ areas from one place to another within Karnal bunt prevailing areas. “
“The aim of this study was to observe the lipid peroxidation (LP) of cell membranes and antioxidant systems in response to inoculation

of Peronospora arborescens causing downy mildew (DM) in opium poppy. Contents of the LP product, malondialdehyde (MDA) and antioxidant glutathione (GSH) were determined in leaves of two opium poppy genotypes, Pps-1 (highly resistant to DM) and Jawahar-16 (highly susceptible to DM) at different time intervals after inoculation (12 h, 24 h, 48 h and 72 h). The provided GSH content corresponded to that of total non-protein sulfhydryl groups. In leaves of Jawahar-16, a significant decrease in concentration of GSH and a persistent increase in concentration of MDA were recorded after inoculation in comparison to leaves of control plants. The continuous decrease

in GSH content contributed to damage of cell membranes leading to disease development in Jawahar-16. On the other hand in a resistant genotype (Pps-1), initially at 12 h after inoculation (hai) the level of GSH was found to be high, but a transient and highly significant decrease in content of GSH and increase in content of MDA was observed at 24 hai in comparison to control plants of same genotype and also in comparison to inoculated plants of susceptible genotype (Jawahar-16). These results indicate that generation MCE公司 of GSH and MDA is negatively correlated during the infection process as found in the case of DM-resistant genotype Pps-1 at 24hai, which also suggests an increased need by the host plant for oxidative stress, required for hypersensitive response mediated defense mechanism. “
“Southern rice black-streaked dwarf virus (SRBSDV) causes southern rice black-streaked dwarf and maize rough dwarf diseases, which lead to severe yield losses of crops in Southeast Asia. We report here a SYBR Green I-based One-Step Real Time RT-PCR assay for quantifying SRBSDV in rice rapidly and accurately.

Through KEGG, 46 and AZD1152-HQPA solubility dmso 41 enriched pathways were collected for the target genes of upregulated and downregulated miRNA, including apoptosis, fatty acid metabolism and so on. Analysis of common target genes of all

downregulated miRNA revealed potential involvement of ion transport and the membrane structure in steatohepatitis. Conclusion:  We reported the dysregulated miRNA in transition from hepatic steatosis to steatohepatitis and showed potential clinical application in disease differentiation. This study provided data reservoir for miRNA exploration and revealed novel disease-specific Gene Ontology functions and KEGG pathways such as uncoupling-protein-guided membrane change. Our data contributes to further researches on the pathogenesis and treatment of non-alcoholic steatohepatitis. “
“Drinking excessive amounts of alcohol regularly for years is toxic to almost every tissue of the body. On the other hand, epidemiological and clinical evidence shows that light-to-moderate drinking is associated with a reduced risk of coronary heart disease, total and ischemic stroke, and mortality. In the past two decades, metabolic syndrome, the combination of obesity, hypertension, dyslipidemia and hyperglycemia, are all also recognized DAPT ic50 as major cardiovascular risk factors, has given rise to much

clinical and research attention, because of its high prevalence in the world. Therefore, it is of interest to evaluate the overall associations of alcohol consumption with the development of metabolic MCE公司 syndrome. Recently, the protective, detrimental or J-shaped associations have been reported between alcohol consumption and metabolic syndrome. This controversy may be due to the complex mechanistic relation between alcohol consumption and each component of metabolic syndrome, and almost all studies have various

limitations and problem points. Prospective studies are therefore needed to confirm the association between alcohol consumption and prevalence of metabolic syndrome, and to assess the influence of alcohol drinking patterns and other possible factors, such as smoking, physical activity, socioeconomic status, education, occupation, diet and exercise. This article reviews the relation of alcohol consumption and components of metabolic syndrome, and discusses the epidemiological evidence for alcohol’s putative vascular protective effects and plausible underlying biological mechanisms. “
“Background and Aim:  Despite improvements of treatment in hepatocellular carcinoma (HCC), the recurrence rate after curative hepatic resection still remains remarkably high. An immediate recurrence of HCC after surgery is frustrating. We tried to clarify risks of immediate postoperative recurrence of HCC; that is, within 4 months after curative hepatic resection.

3A). Albeit remarkable, these differences were not statistically different.

Similarly, a slight up-regulation of tumor necrosis factor α mRNA (two-fold to six-fold) was detected in Mcl-1Δhep mice compared to WT and Mcl-1flox/wt mice (data not shown). In contrast, mRNA levels of interleukin 1β (IL1β and interferon gamma (IFNγ) were not different (Fig. 3A). Remarkably, livers of Mcl-1Δhep mice revealed scattered cells immunoreactive for the cytokine TGFβ, an important inducer of carcinogenesis, which were not detectable in control mice (Fig. 3B). Next, we addressed whether the relative increase of liver weight in Mcl-1Δhep animals and the strong up-regulation of Survivin might be linked to a higher hepatocyte proliferation rate, which we had observed previously in 4-month-old mice.10 Indeed, GDC-0449 nmr Mcl-1Δhep mice revealed a highly significant increase of Ki67+ hepatocytes compared to WT and heterozygous Mcl-1flox/wt mice at the age

of 8 and 12 months (P GPCR Compound Library < 0.0001, and P < 0.001, respectively; Fig. 3C). Remarkably, heterozygous Mcl-1flox/wt livers also displayed increased proliferation indices compared to WT livers. Quantification by BrdU incorporation corroborated this finding: Livers of 8-month-old Mcl-1Δhep mice still showed a significantly higher proliferation rate when compared to age-matched heterozygous Mcl-1flox/wt mice (P < 0.05; Fig. 3D). WT and heterozygous Mcl-1flox/wt mice revealed macroscopically normal livers at the age of 8 and 12 months. This was in contrast to age-matched Mcl-1Δhep livers which contained tumors in >50% of Mcl-1Δhep livers (Table 1). Liver tumors ranged from ∼2 mm to 3 cm in diameter (Fig. 4A). In addition, nontumorous parts of Mcl-1Δhep livers revealed a spectrum of findings ranging from a macroscopically unremarkable (some animals) to a strongly nodular (most animals) structure (Fig. 3A). Histologic analysis confirmed that ∼50% of all Mcl-1Δhep mice (11/21) 上海皓元医药股份有限公司 displayed liver tumors (Fig. 4B). Larger tumors showed cellular atypia, altered liver-architecture

with broadening of liver cell cords (highlighted by collagen IV staining), and loss of reticulin fibers (shown by Gomori staining). In addition, the proliferation rate again increased compared to nontumorous areas, and a focal pattern of strong immunoreactivity for glutamine synthetase was observed (Fig. 4C). These findings support that the tumors histologically qualified as HCC. Mcl-1–deficient livers displayed different staining patterns for the oval cell marker A6. Mostly, tumors and nontumorous tissues were A6-negative (A6−). However, in several instances A6+ tumors, surrounded by A6− liver tissue, were detected. Besides, we could also detect one A6− tumor surrounded by A6+ liver tissue (Fig. 4D).

3A). Albeit remarkable, these differences were not statistically different.

Similarly, a slight up-regulation of tumor necrosis factor α mRNA (two-fold to six-fold) was detected in Mcl-1Δhep mice compared to WT and Mcl-1flox/wt mice (data not shown). In contrast, mRNA levels of interleukin 1β (IL1β and interferon gamma (IFNγ) were not different (Fig. 3A). Remarkably, livers of Mcl-1Δhep mice revealed scattered cells immunoreactive for the cytokine TGFβ, an important inducer of carcinogenesis, which were not detectable in control mice (Fig. 3B). Next, we addressed whether the relative increase of liver weight in Mcl-1Δhep animals and the strong up-regulation of Survivin might be linked to a higher hepatocyte proliferation rate, which we had observed previously in 4-month-old mice.10 Indeed, RAD001 Mcl-1Δhep mice revealed a highly significant increase of Ki67+ hepatocytes compared to WT and heterozygous Mcl-1flox/wt mice at the age

of 8 and 12 months (P PXD101 < 0.0001, and P < 0.001, respectively; Fig. 3C). Remarkably, heterozygous Mcl-1flox/wt livers also displayed increased proliferation indices compared to WT livers. Quantification by BrdU incorporation corroborated this finding: Livers of 8-month-old Mcl-1Δhep mice still showed a significantly higher proliferation rate when compared to age-matched heterozygous Mcl-1flox/wt mice (P < 0.05; Fig. 3D). WT and heterozygous Mcl-1flox/wt mice revealed macroscopically normal livers at the age of 8 and 12 months. This was in contrast to age-matched Mcl-1Δhep livers which contained tumors in >50% of Mcl-1Δhep livers (Table 1). Liver tumors ranged from ∼2 mm to 3 cm in diameter (Fig. 4A). In addition, nontumorous parts of Mcl-1Δhep livers revealed a spectrum of findings ranging from a macroscopically unremarkable (some animals) to a strongly nodular (most animals) structure (Fig. 3A). Histologic analysis confirmed that ∼50% of all Mcl-1Δhep mice (11/21) medchemexpress displayed liver tumors (Fig. 4B). Larger tumors showed cellular atypia, altered liver-architecture

with broadening of liver cell cords (highlighted by collagen IV staining), and loss of reticulin fibers (shown by Gomori staining). In addition, the proliferation rate again increased compared to nontumorous areas, and a focal pattern of strong immunoreactivity for glutamine synthetase was observed (Fig. 4C). These findings support that the tumors histologically qualified as HCC. Mcl-1–deficient livers displayed different staining patterns for the oval cell marker A6. Mostly, tumors and nontumorous tissues were A6-negative (A6−). However, in several instances A6+ tumors, surrounded by A6− liver tissue, were detected. Besides, we could also detect one A6− tumor surrounded by A6+ liver tissue (Fig. 4D).

The microenvironment drives the cells rapidly to a specific adult fate that can be easily identified by morphology and functions. Further differentiation occurs with or without selective pressure in vivo. That for lineage restriction toward the intrahepatic parenchymal cell fates resulted in rapid differentiation, because the in vivo environment is toward integration of the cells within the liver plates followed by differentiation and with minimal adverse variables. check details By contrast, that for pancreatic islets in hosts with STZ-induced diabetes involved selective pressure for differentiation in combination

with adverse effects of the toxic environment induced by hyperglycemia. Blood vessels can become narrowed or blocked by a buildup of fat and cholesterol due to abnormal glucose metabolism and poor nutrient conditions in hyperglycemic environment. Transplanted precursors for pancreatic islets selleck chemicals llc can take months to fully mature given this mix of positive and negative effects resulting from hyperglycemia, as has been shown by others.28 Thus, the speed

of differentiation achieved in vitro versus in vivo is distinct for each adult fate being generated and dependent on the balance of positive and adverse effects of the in vivo microenvironment. We interpret the survival and rescue of the transplanted mice from hyperglycemia as due to the production of human insulin. One cannot exclude the possibility that some degree of spontaneous regeneration of MCE the mouse pancreas might have occurred, resulting in the regeneration of endogenous islets releasing murine insulin, but even if this occurred it was insufficient to rescue the sham controls. The controls subjected to STZ maintained glucose levels above 750 mg/dL throughout the experiments, and some of them died. One cannot consider the option of formation of hybrids between host pancreatic islet cells and the biliary tree-derived islet-like clusters,

because transplantation was done into the fat pads. The strongest evidence is that the dramatic reduction in hyperglycemia in the experimental mouse correlated with increasing levels of human insulin/C-peptide in their blood, and that the levels were regulatable by glucose injected into the mice. The extent of response observed seems logical given that low numbers of partially differentiated neoislet-like clusters were implanted; given the poor nutrient environment for the grafts due to the high blood glucose levels; and given that mouse cells are far less sensitive to human insulin than mouse insulin. We assume that a normoglycemic state would be achieved within the time frame we used if higher numbers of neoislets were transplanted.

15 It was originally proposed that liver stem cells, or oval cells, have the capacity to regenerate the liver during these times of chronic liver injury.37, 38 Recently, Amin and Mishra20 proposed a refinement of this oval cell model, where activated liver stem cells acquire resistance to TGFβ-induced cell growth inhibition and differentiation, and thus are able to escape the normal cell cycle control and undergo malignant transformation. During chronic liver diseases, TGFβ is secreted by nonparenchymal cells such as hepatic stellate cells and acts as a stimulator of extracellular matrix production, resulting in fibrosis and

cirrhosis.17 Nearly 95% of HCC is developed in a cirrhotic liver in chronic hepatitis C infection and almost 60% during chronic hepatitis B.17 As a profibrotic growth

factor in liver, TGFβ acts as an inhibitor of hepatocyte proliferation; however, the exact role of TGFβ in HCC AZD4547 initiation and progression remains controversial. It is believed that TGFβ inhibits carcinogenesis at the early stage and acts as a promoter of cancer progression at the later stage disease.39 Increased hepatocarcinogenesis from stem cells through disruption of TGFβ and IL-6 signaling provided additional evidence of the association between TGFβ and HCC.32 Some studies revealed that cellular stress, hypoxia, for example, and the mTOR signal pathway, are able to induce CD133 expression in cancer cells.27, 40 This finding indicated that CD133 expression in liver cells 上海皓元 may be in response to microenvironmental alterations. For example, in a cirrhotic liver the cells are exposed to a microenvironment abundant in TGFβ. Therefore, we postulated Pexidartinib that elevated TGFβ might be able to trigger CD133 transcription. In our current findings we demonstrated that TGFβ1 was capable of inducing CD133 expression in CD133− Huh7 cells. Although TGFβ1-induced CD133+ Huh7 cells were less tumorigenic than that of native CD133+ Huh7 cells, the induced CD133+ cells were characterized as significantly more

tumorigenic than native CD133− cells in vivo. These findings might serve as an additional link between TGFβ and malignant transformation in chronic liver injury. A previous publication demonstrated that CD133 expression is controlled by five alternative promoters, with promoter-1 and -2 active in liver tissue.26 CD133 promoter-1 and -2 are located in a CpG island, indicating that CD133 transcription in the liver may be regulated by epigenetic modification through promoter methylation status. Promoter methylation is an important mechanism that leads to gene transcriptional silencing. CpG hypermethylation in promoter regions of tumor suppressors has been linked to tumorigenesis.21, 22 For example, Ras and downstream Ras effectors were activated due to epigenetic silencing of inhibitors of the Ras pathway in HCC.41 In terms of CD133, recent reports indicate that expression is inversely correlated with promoter methylation.

15 It was originally proposed that liver stem cells, or oval cells, have the capacity to regenerate the liver during these times of chronic liver injury.37, 38 Recently, Amin and Mishra20 proposed a refinement of this oval cell model, where activated liver stem cells acquire resistance to TGFβ-induced cell growth inhibition and differentiation, and thus are able to escape the normal cell cycle control and undergo malignant transformation. During chronic liver diseases, TGFβ is secreted by nonparenchymal cells such as hepatic stellate cells and acts as a stimulator of extracellular matrix production, resulting in fibrosis and

cirrhosis.17 Nearly 95% of HCC is developed in a cirrhotic liver in chronic hepatitis C infection and almost 60% during chronic hepatitis B.17 As a profibrotic growth

factor in liver, TGFβ acts as an inhibitor of hepatocyte proliferation; however, the exact role of TGFβ in HCC selleck chemicals initiation and progression remains controversial. It is believed that TGFβ inhibits carcinogenesis at the early stage and acts as a promoter of cancer progression at the later stage disease.39 Increased hepatocarcinogenesis from stem cells through disruption of TGFβ and IL-6 signaling provided additional evidence of the association between TGFβ and HCC.32 Some studies revealed that cellular stress, hypoxia, for example, and the mTOR signal pathway, are able to induce CD133 expression in cancer cells.27, 40 This finding indicated that CD133 expression in liver cells medchemexpress may be in response to microenvironmental alterations. For example, in a cirrhotic liver the cells are exposed to a microenvironment abundant in TGFβ. Therefore, we postulated LY2157299 that elevated TGFβ might be able to trigger CD133 transcription. In our current findings we demonstrated that TGFβ1 was capable of inducing CD133 expression in CD133− Huh7 cells. Although TGFβ1-induced CD133+ Huh7 cells were less tumorigenic than that of native CD133+ Huh7 cells, the induced CD133+ cells were characterized as significantly more

tumorigenic than native CD133− cells in vivo. These findings might serve as an additional link between TGFβ and malignant transformation in chronic liver injury. A previous publication demonstrated that CD133 expression is controlled by five alternative promoters, with promoter-1 and -2 active in liver tissue.26 CD133 promoter-1 and -2 are located in a CpG island, indicating that CD133 transcription in the liver may be regulated by epigenetic modification through promoter methylation status. Promoter methylation is an important mechanism that leads to gene transcriptional silencing. CpG hypermethylation in promoter regions of tumor suppressors has been linked to tumorigenesis.21, 22 For example, Ras and downstream Ras effectors were activated due to epigenetic silencing of inhibitors of the Ras pathway in HCC.41 In terms of CD133, recent reports indicate that expression is inversely correlated with promoter methylation.

We obtained three selleck chemicals founders (TG-8, TG-9, and TG-15) with serum levels of IL-22 reaching ≈6,000 pg/mL. All of the experiments described below were obtained from the TG-8 founder (referred to as IL-22TG). Many of these experiments were confirmed using TG-9 or TG-15, thus demonstrating that our findings are due to the transgene, not the unique founder line of mice. Figure 2A shows that high levels of serum IL-22 were detected in the three founders of transgenic lines but not in wild-type (WT)

mice. Serum levels of IL-22 were detected as early as 2 weeks in IL-22TG after birth and reached the peak level (≈6,000 pg/mL) at 1 month (Fig. 2B). Such levels of serum IL-22 were maintained for the lifetime of mice and did not change during the backcrossing with C57BL/6 mice. IL-22 is known to induce expression of acute phase proteins (e.g., serum

amyloid A [SAA]) and multiple signaling pathways in hepatocytes.2, BYL719 solubility dmso 20 Here we observed that IL-22TG mice had a trend to higher levels of serum SAA compared with WT mice, with a statistical difference being reached at age 2 months (Fig. 2B). In addition, microarray data revealed that hepatic RNA expression of SAA, as well as several other acute phase proteins, were elevated in IL-22TG mice versus WT mice (Table 1). All IL-22TG mice grew normally without obvious adverse phenotypes except a lower body weight after 5 months of age compared with WT mice (Fig. 2C). Food intake was similar in both IL-22TG and WT mice (data not shown). In addition, at 2 months of age, both IL-22TG and WT mice had 上海皓元医药股份有限公司 a similar liver weight and liver/body weight ratio; at 5 months of age, IL-22TG mice had similar liver weights but a higher liver/body weight ratio compared with WT mice. In contrast, at 12 months of age, IL-22TG mice had a lower liver weight but similar liver/body weight ratio compared with WT mice. Western blot analyses

revealed that phosphorylated STAT3 (pSTAT3) but not pSTAT1 or extracellular signal-regulated kinase 1/2 activation was elevated in the livers of IL-22TG mice versus WT mice (Fig. 2D). Activation of pSTAT3 was also detected in the kidney but not the spleen from IL-22TG mice (Fig. 2D), indicating that the circulating IL-22 had effects beyond the tissue in which it is being produced. The lack of effects in the spleen was not surprising, as normal mouse lymphocytes/leukocytes lack IL-22R1.4 Histology analyses showed that all of the organs from IL-22TG mice had a normal histology except for slightly thicker epidermis and minor inflammation in the skin compared with WT mouse skin (Fig. 2E, Supporting Information Fig. 2a). No obvious inflammation or necrosis was observed in the organs obtained from IL-22TG mice.