TLR7 gain-of-function genetic variation causes human lupus.

Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease1-7, evidence of lupus-causing TLR7 gene variants is lacking. Here we describe human systemic lupus erythematosus caused by a TLR7 gain-of-function variant. TLR7 is a sensor of viral RNA8,9 and binds to guanosine10-12. We identified a de novo, previously undescribed missense TLR7Y264H variant in a child with severe lupus and additional variants in other patients with lupus. The TLR7Y264H variant selectively increased sensing of guanosine and 2',3'-cGMP10-12, and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c+ age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7Y264H mice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.

Monogenic lupus: insights into disease pathogenesis and therapeutic opportunities.

PURPOSE OF REVIEW: This review aims to provide an overview of the genes and molecular pathways involved in monogenic lupus, the implications for genome diagnosis, and the potential therapies targeting these molecular mechanisms. RECENT FINDINGS: To date, more than 30 genes have been identified as contributors to monogenic lupus. These genes are primarily related to complement deficiency, activation of the type I interferon (IFN) pathway, disruption of B-cell and T-cell tolerance and metabolic pathways, which reveal the multifaceted nature of systemic lupus erythematosus (SLE) pathogenesis. SUMMARY: In-depth study of the causes of monogenic lupus can provide valuable insights into of pathogenic mechanisms of SLE, facilitate the identification of effective biomarkers, and aid in developing therapeutic strategies.

The silk gland proteome of Stenopsyche angustata provides insights into the underwater silk secretion.

Caddisworms (Trichoptera) spin adhesive silks to construct a variety of underwater composite structures. Many studies have focused on the fibroin heavy chain of caddisworm silk and found that it contains heavy phosphorylation to maintain a stable secondary structure. Besides fibroins, recent studies have also identified some new silk proteins within caddisworm silk. To better understand the silk composition and its secretion process, this study reports the silk gland proteome of a retreat-building caddisworm, Stenopsyche angustata Martynov (Trichoptera, Stenopsychidae). Using liquid chromatography tandem mass spectrometry (LC-MS/MS), 2389 proteins were identified in the silk gland of S. angustata, among which 192 were predicted as secreted silk proteins. Twenty-nine proteins were found to be enriched in the front silk gland, whereas 109 proteins were enriched in the caudal silk gland. The fibroin heavy chain and nine uncharacterized silk proteins were identified as phosphorylated proteins. By analysing the sequence of the fibroin heavy chain, we found that it contains 13 Gly/Thr/Pro-rich regions, 12 Val/Ser/Arg-rich regions and a Gly/Arg/Thr-rich region. Three uncharacterized proteins were identified as sericin-like proteins due to their larger molecular weights, signal peptides and repetitive motifs rich in serine. This study provides valuable information for further clarifying the secretion and adhesion of underwater caddisworm silk.

Pregnancy-related intracranial venous sinus thrombosis secondary to cryptococcal meningoencephalitis: a case report and literature review.

BACKGROUND: Cerebral venous sinus thrombosis (CVST), a serious cerebrovascular and neurological emergency, is common in pregnant individuals and accounts for approximately 0.5-1.0% of all cerebrovascular diseases. However, CVST with cryptococcal meningoencephalitis in immunocompetent pregnant patients is rare. CASE PRESENTATION: A 30-year-old woman who was 33 weeks pregnant presented with recurrent dizziness, headache, and vomiting as the main clinical manifestations, all of which were initially nonspecific. After assessment of the cerebrospinal fluid, skull computerized tomography, magnetic resonance imaging, and other laboratory and imaging examinations, the patient was diagnosed with secondary pregnancy-related CVST with cryptococcal meningoencephalitis. Despite receiving potent anticoagulant and antifungal treatment, the patient's condition deteriorated, and the patient's family opted to cease treatment. CONCLUSIONS: We present a rare case of CVST with cryptococcal meningoencephalitis in an immunocompetent pregnant patient. The difficulty of diagnosing and treating secondary pregnancy-related CVST caused by cryptococcal meningoencephalitis, as well as the great challenges faced at present are highlighted. One crucial lesson from the present case is that when clinical and imaging signs are unusual for CVST during pregnancy, it is essential to account for the possibility of other central nervous system (CNS) diseases, such as CNS infections with Cryptococcus, which may cause CVST.

Immune defense adaptation of Strauchbufo raddei population in heavy metal polluted area: Insights from developmental and environmental perspectives.

The adjustment of immune defense mechanisms is a crucial aspect of biological adaptation to stressful environments. Amphibians, with their unique metamorphic process, experience distinct life stages and exhibit diverse immune defense components. While previous studies have focused on specific immune changes during particular life stages under stress, this research addresses a critical gap by exploring the adaptive immune defense strategies of Strauchbufo raddei in heavy metal-polluted environments. We conducted laboratory experiments, exposing offspring from both polluted and unpolluted areas to control and heavy metal treatments, while continuously monitoring changes in immune components during key metamorphic stages. Notably, we examined the role of the skin microbiome, a crucial but often overlooked barrier against pathogens. The results indicated that individuals from polluted areas exhibited some tolerance to heavy metal exposure, though overall immune function remained diminished. During metamorphosis, when immune defenses are most vulnerable, the skin microbiome rapidly enriched beneficial bacteria, preventing pathogenic colonization and playing a pivotal role in maintaining immune defense in contaminated environments. Moreover, our research highlights energy allocation strategies involving corticosterone and body fat content, enabling populations to maintain development despite immune compromise. The immune adaptations observed may be fixed through genetic assimilation, suggesting a rapid evolutionary response to environmental stress. However, this reduces phenotypic plasticity, making populations more vulnerable to future environmental changes. This study provides key insights into the survival strategies of amphibian populations in heavy metal-contaminated areas, laying the foundation for future research on molecular and evolutionary adaptations.

Multi-omics analysis of functional substances and expression verification in cashmere fineness.

BACKGROUND: Numerous factors influence the growth and development of cashmere. Existing research on cashmere has predominantly emphasized a single omics level. Integrating multi-omics analyses can offer a more comprehensive understanding by encompassing the entire spectrum. This study more accurately and comprehensively identified the key factors influencing cashmere fineness using multi-omics analysis. METHODS: This study used skin tissues of coarse cashmere type (CT_LCG) and fine cashmere type Liaoning cashmere goats (FT_LCG) for the analysis. This study employed an integrated approach involving transcriptomics, translatomics, proteomics, and metabolomics to identify substances associated with cashmere fineness. The findings were validated using parallel reaction monitoring (PRM) and multiple reaction monitoring (MRM) techniques. RESULTS: The GO functional enrichment analysis identified three common terms: multicellular organismal process, immune system process, and extracellular region. Furthermore, the KEGG enrichment analysis uncovered the involvement of the arachidonic acid metabolic pathway. Protein expression trends were verified using PRM technology. The expression trends of KRT79, as confirmed by PRM, were consistent with those observed in TMT proteomics and exhibited a positive regulatory effect on cashmere fineness. Metabolite expression trends were confirmed using MRM technology. The expression trends of 9 out of 15 validated metabolites were in agreement with those identified in the non-targeted metabolomics analysis. CONCLUSIONS: This study employed multi-omics analysis to identify key regulators of cashmere fineness, including PLA2G12A, KRT79, and prostaglandin B2. The findings of this study offer valuable data and establish a theoretical foundation for conducting comprehensive investigations into the molecular regulatory mechanisms and functional aspects of cashmere fineness.

Biogenetic Vesicle-Based Cancer Vaccines with Tunable Surface Potential and Immune Potency.

Cancer vaccines are designed to motivate antigen-specific immune responses and facilitate tumor regression with minimal side effects. To fully exert the potential of vaccines, rationally designed formulations that effectively deliver antigens and trigger potent immune reactions are urgently needed. This study demonstrates a simple and controllable vaccine-developing strategy that assembles tumor antigens into bacterial outer membrane vesicles (OMVs), natural delivery vehicles with intrinsic immune adjuvant properties, via electrostatic interaction. This OMV-delivered vaccine (OMVax) stimulated both innate and adaptive immune responses, leading to enhanced metastasis inhibition and prolonged survival of tumor-bearing mice. Moreover, the influence of different surface charged OMVax on antitumor immunity activation is investigated and declined immune response activation occurred with increased positive surface charge. Together, these findings suggest a simple vaccine formulation that can be enhanced by optimizing the surface charges of vaccine formulations.

Transcriptomics analysis of cashmere fineness functional genes.

Liaoning cashmere goat (LCG) is a famous cashmere goat breed in China. Cashmere fineness, as an important index to evaluate cashmere quality, is also one of the problems to be improved for Liaoning cashmere goats. Transcriptome studies all mRNA transcribed by a specific tissue or cell in a certain period. It is a key link in the study of gene expression regulation. It plays an important role in the analysis of biological growth and disease. Transcriptome is spatio-temporal specific, that is, gene expression varies in different tissues or at different times. Three coarser and three fine LCG skin samples were sequenced by RNA-seq technology, and a total of 427 differentially expressed genes were obtained, including 291 up-regulated genes and 136 down-regulated genes. In the experiment, we screened out 16 genes that had significant differences in the expression of coarse and fine cashmere of Liaoning cashmere goats, so it was inferred that these 16 genes might have regulatory effects on cashmere fineness. Moreover, GO gene set enrichment analysis revealed that differential genes mainly consist of immune response, MHC protein complex, Heme binding and other pathways. KEGG analysis showed that transplant-versus-host disease and allograft rejection were the main pathways of differential genes.

Association analysis for SNPs of BAAT and COL1A1 genes with cashmere production performance and other production traits in Liaoning cashmere goats.

This study aimed to investigate the relationship between the polymorphism of bile acid-CoA: amino acid N-acyltransferase (BAAT) and collagen type I alpha 1 chain (COL1A1) genes and the production performance of Liaoning Cashmere goat (LCG). The potential single nucleotide polymorphisms (SNPs) of LCG were detected by sequence comparison of BAAT and COL1A1 genes and PCR-Seq polymorphism, and the effect of SNPs on production performance was analyzed by SPSS software. The results showed that three SNPs loci were detected in BAAT gene: G7900A, T7967C, C7998T, and one SNP locus T6716C was detected in COL1AL gene. At G7900A locus, the dominant genotype for cashmere performance was GG, and the dominant genotype for body measurement traits and milk production traits was AG. At T7967C locus, the dominant genotype for cashmere performance was TT, and the dominant genotype for body measurement traits and milk production traits was CC. At C7998T locus, TT was the dominant genotype for cashmere performance, body measurement traits, and milk production traits. At the T6716C locus, TT was the dominant genotype for cashmere performance, body measurement traits, and milk production traits. H1H1: AACC is the dominant haplotype combination. Therefore, this study will provide a reliable reference for future research on cashmere production performance, body measurement traits, and milk production traits of LCG.

Association analysis for SNPs of LIPE and ITGB4 genes with cashmere production performance, body measurement traits and milk production traits in Liaoning cashmere goats.

Liaoning cashmere goat (LCG) is one of the excellent cashmere goat breeds in China. Because of its larger size, better cashmere, and better cashmere production performance, people pay special attention to it. This article mainly studied the relationship between SNP loci of LIPE gene and ITGB4 gene and milk production, cashmere production and body measurement traits of LCGs. We further identified potential SNP loci by PCR-Seq polymorphism detection and gene sequence comparison of LIPE and ITGB4 genes. Further, we use SPSS and SHEsis software to analyze their relationship to production performance. The consequence indicated that CC genotype of LIPE gene T16409C locus was dominant genotype in milk production and cashmere production, while CT genotype of LIPE gene T16409C locus was dominant in body size. The CT genotype of C168T locus of ITGB4 gene is the dominant genotype of body type and cashmere production, while the dominant genotype of milk production is TT genotype. Through joint analysis, in haploid combinations, H1H2:CCCT is the dominant haplotype combination in cashmere fineness. H3H4:TTCT is a dominant haplotype combination of milk production traits and body measurement traits. These dominant genotypes can provide a reliable basis for the study of production performance of LCG.

Association analysis for SNPs of KRT26 and TCHH genes with cashmere production performance, body measurement traits and milk production traits in Liaoning cashmere goats.

Cashmere fineness is getting thicker, which is one of the key problems in cashmere breeding, however, there have been no systematic studies on the molecular regulation of cashmere fineness. The aim of this study was to investigate the relationship between KRT26 and TCHH gene polymorphism and production performance in Liaoning cashmere goats (LCG). The potential single nucleotide polymorphisms (SNPs) of LCG were detected by sequence alignment and PCR-Seq polymorphism of KRT26 and TCHH genes and analyzed the effect of SNPs on production performance by SPSS software. Two SNPs sites (A559T and A6839G) of two genes were detected. The AA genotype of KRT26 A559T locus was the dominant genotype. AG and GG at TCHH A6839G locus were the dominant genotypes. AAAA was the dominant haplotype combination. The results showed that KRT26 and TCHH genes were associated with cashmere fineness of LCG, and A559T (AA) and A6839G (GG) genotypes were the preferred marker genotypes for cashmere fineness, which provided more theoretical basis for further research on cashmere fineness.

Association analysis for SNPs of MSTN and IGFBP-3 genes with body size and other production traits in Liaoning Cashmere Goats.

Liaoning cashmere goat (LCG) have tall bones, high cashmere production and outstanding meat production performance. In recent years, good breeding progress has not been made in terms of body size, meat yield, milk yield and other properties in terms of production. The study focused on the correlation between the SNPs of MSTN and IGFBP-3 genes with the body size performance, cashmere production and milk performance. The MSTN and IGFBP-3 gene sequence alignment and PCR-Seq polymorphism were used to detect the potential SNPs, and the correlation with production performance was analyzed by SPSS and SHEsis software. The results showed that the TT genotype at the T1662G locus of the MSTN gene is dominant and has significant advantages in body measurements such as sacrum height, chest width, and waist height. The C allele at the C4021T locus of IGFBP-3 gene shows an advantage in the body measurement performance. Among the haplotype combinations, H2H2:TGTC is preponderant combination for body size performance, H2H2:TGTC and H1H2:TGCC are preponderant combinations for cashmere production performance, H1H3:GGCC is preponderant combination for milk production performance. It may be a molecular marker for future selection and breeding.

Proteomic analysis of coarse and fine skin tissues of Liaoning cashmere goat.

Proteomics is the study of all proteins expressed by a cell or even an organism. However, knowledge of proteins that regulate the fineness of cashmere is limited. Liaoning cashmere goat (LCG) is a valuable genetic resource of China. The skin samples of Liaoning cashmere goats during the growing period were collected, performed tandem mass tag (TMT) method, and identified 117 differentially expressed proteins in CT_LCG (course type) and FT_LCG (fine type). To verify proteins differentially expressed in LCG, we performed PRM validation on three candidate proteins (ALB, SDC1, and ITGB4) in CT-LCG and FT-LCG. Furthermore, primary metabolic process and lysosome are most enriched in the GO and KEGG pathways, respectively. In addition, we also derived a protein-protein interaction (PPI) regulatory network from the perspective of bioinformatics. This study sought to elucidate the molecular mechanism of differential proteins regulating cashmere fineness of Liaoning cashmere goats by using TMT quantitative proteomics analysis. Differentially expressed proteins ALB and SDC1 may regulate cashmere fineness; ITGB4 can become a promising protein for further study. They can be used as key proteins to lay a foundation for studying cashmere fineness of Liaoning cashmere goats.

iRhom2 Promotes Hepatic Steatosis by Activating MAP3K7-Dependent Pathway.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) has been widely recognized as a precursor to metabolic complications. Elevated inflammation levels are predictive of NAFLD-associated metabolic disorder. Inactive rhomboid-like protein 2 (iRhom2) is regarded as a key regulator in inflammation. However, the precise mechanisms by which iRhom2-regulated inflammation promotes NAFLD progression remain to be elucidated. APPROACH AND RESULTS: Here, we report that insulin resistance, hepatic steatosis, and specific macrophage inflammatory activation are significantly alleviated in iRhom2-deficient (knockout [KO]) mice, but aggravated in iRhom2 overexpressing mice. We further show that, mechanistically, in response to a high-fat diet (HFD), iRhom2 KO mice and mice with iRhom2 deficiency in myeloid cells only showed less severe hepatic steatosis and insulin resistance than controls. Inversely, transplantation of bone marrow cells from healthy mice to iRhom2 KO mice expedited the severity of insulin resistance and hepatic dyslipidemia. Of note, in response to HFD, hepatic iRhom2 binds to mitogen-activated protein kinase kinase kinase 7 (MAP3K7) to facilitate MAP3K7 phosphorylation and nuclear factor kappa B cascade activation, thereby promoting the activation of c-Jun N-terminal kinase/insulin receptor substrate 1 signaling, but disturbing AKT/glycogen synthase kinase 3ß-associated insulin signaling. The iRhom2/MAP3K7 axis is essential for iRhom2-regulated liver steatosis. CONCLUSIONS: iRhom2 may represent a therapeutic target for the treatment of HFD-induced hepatic steatosis and insulin resistance.

Association between the cashmere production performance, milk production performance, and body size traits and polymorphism of COL6A5 and LOC102181374 genes in Liaoning cashmere goats.

The purpose of this study was to analyze the relationship between COL6A5 (collagen type VI alpha 5 chain) and LOC102181374 (alcohol dehydrogenase 1) genes and the production performance of Liaoning cashmere goats by single nucleotide polymorphism (SNP). We have searched for SNP loci of COL6A5 and LOC102181374 genes through sequence alignment and PCR experiments, and have used SPSS and SHEsis software to analyze production data. We obtained five SNP loci in total, including three SNP loci (G50985A, G51140T, G51175A) in COL6A5 gene and two SNP loci (A10067G, T10108C) in LOC102181374 gene. The genotypes G50985A (AG), G51140T (GT), G51175A (AA), A10067G (AA), and T10108C (CC) of these loci have certain advantages in improving the production performance of Liaoning cashmere goats. The haplotype combinations that can improve production performance in COL6A5 gene were H1H5:AGGGAG, H4H4:GGGGAA, and H4H4:GGGGAA. H3H3:GGCC and H2H4:AGTT were the dominant combinations in LOC102181374 gene. At G51175A and A10067G loci, we found that H1H2:AAAG and H1H3:AGAA have dominant effects. These results may provide some support for the molecular breeding of production traits in Liaoning cashmere goats.

Metabolomic Analysis and MRM Verification of Coarse and Fine Skin Tissues of Liaoning Cashmere Goat.

One of the critical elements in evaluating the quality of cashmere is its fineness, but we still know little about how it is regulated at the metabolic level. In this paper, we use UHPLC-MS/MS detection and analysis technology to compare the difference in metabolites between coarse cashmere (CT_LCG) and fine cashmere (FT_LCG) skin of Liaoning cashmere goats. According to the data, under positive mode four metabolites were significantly up-regulated and seven were significantly down-regulated. In negative mode, seven metabolites were significantly up-regulated and fourteen metabolites were significantly down-regulated. The two groups' most significant metabolites, Gly-Phe and taurochenodeoxycholate, may be crucial in controlling cashmere's growth, development, and fineness. In addition, we enriched six KEGG pathways, of which cholesterol metabolism, primary bile acid biosynthesis, and bile secretion were enriched in positive and negative modes. These findings offer a new research idea for further study into the critical elements influencing cashmere's fineness.

Functional characterization of an interleukin 20 like homologue in grass carp Ctenopharyngodon idella.

IL-20 is a pleiotropic cytokine that belongs to the IL-10 family and plays an important biological role in tissue homeostasis and regulation of host immune defenses. IL-20 homologues have recently been discovered in fish, but their functions have not been studied. In this study, an IL-20 like (IL-20L) cytokine was cloned in grass carp (Ctenopharyngodon idella) and its bioactivities were investigated. Expression analysis showed that the CiIL-20L gene was constitutively expressed in tissues with the highest expression detected in the head kidney. It was upregulated in the head kidney after infection with Flavobactrium columnare (F. cloumnare) and grass carp reovirus II (GCRV II). The recombinant CiIL-20L produced in E. coli cells was shown to be effective in inducing the expression of Th cytokine genes (IFN-γ, IL-4/13A, IL-4/13B and IL-10), macrophage marker genes (arginase 2, IRF4, KLF4 and SOCS3) and inflammatory genes (IL-1ß, IL-6, IL-8 and TNFα) in the head kidney leukocytes when stimulated at 12 h. Long term culture (6 days) of head kidney macrophages in the presence of CiIL-20L leads to high expression of IRF4, TGFß1 and arginase 2. Our data suggest that IL-20 may play regulatory roles in promoting Th responses, macrophage differentiation and inflammation.

"Zuòyuèzi" dietary and behavioural associations with maternal health among puerperal women in South China.

BACKGROUND AND OBJECTIVES: This study aimed to explore the associations of postpartum dietary quality and behavioral practices with maternal health in Guangzhou China. METHODS AND STUDY DESIGN: We conducted a cross-sectional study among puerperal women in urban and suburban areas in Guangzhou, China (n=2013). Data for postpartum dietary and behavioral practices and health conditions were collected by a standardized questionnaire. Dietary balance index (DBI) was calculated to assess an individual's dietary quality. Logistic regression analysis was used to identify the factors related to women's health. RESULTS: 75.5% of women reported at least one postpartum disease, and the most common problems were prolonged duration of lochia (70.0%) and backache (43.0%), followed by constipation (23.6%), insufficient milk secretion (19.2%), breast swelling (18.5%) and hemorrhoids (13.8%). Average postpartum weight retention was 3.5 kg. Logistic regression analysis revealed that 12-18 h/d of bed rest time, breastfeeding, doing postpartum exercise, basking, getting out of bed within 2 days after delivery, higher intake of fish and shrimp, fruits, vegetable, milk were protective factors for at least one out of these health problems or weight retention (p<0.05). Bed rest time for more than 18 h/d or less than 12 h/d, ginger vinegar intake, doing housework, cesarean section, and excessive and inadequate intake of cereals had an adverse association (p<0.05). CONCLUSIONS: Some features of a traditional Chinese postpartum diet and behaviour are related to maternal morbidity during the puerperium. Further studies are needed to assess whether postpartum diet and behavioral intervention improve maternal health during the postpartum period.

[Association between the dietary inflammatory index, interleukin-6 of late pregnant women and birth weight].

OBJECTIVE: To explore the relationship between dietary inflammatory index(DII), serum interleukin-6(IL-6) of late pregnant women and infant birth weight. METHODS: This study was conducted in late pregnant women who received antenatal care at the Maternal and Children& apos; s Hospital of Baiyun and Yuexiu District in Guangzhou, China between September 2010 and February 2011. Tree consecutive 24-h diet recalls, pre-pregnancy body mass index, maternal education level and etc were collected. DII score was calculated based on data of dietary surveys. Participant were dived into anti-inflammatory group(T1), neutral group(T2) and pro-inflammatory group(T3) according to the tertiles of DII score. Maternal and infant anthropometric profile(n=456) and level of maternal serum IL-6(n=308) were measured. Structrural equation modeling(SEM) was used to explore the relationship between DII, IL-6 and birth weight. RESULTS: In 456 women, the mean DII score was 0. 02±1. 08. Women performed anti-inflammatory diet had higher intake of grain and potato, vegetables, energy, fiber, minerals, vitamins and unsaturated fatty acids, but lower intakes of fruits, diary, fat(% energy) and protein from animal food(P& lt; 0. 05). Average infant birth weight and level of maternal serum IL-6 were(3238. 1±376. 4)g and 4. 05(2. 02, 10. 14) pg/mL respectively. DII of pregnant women was positively correlated with maternal serum IL-6(r=0. 144, P& lt; 0. 05), and IL-6 was negatively correlated with birth weight(r=-0. 184, P& lt; 0. 05). SEM indicated that maternal serum IL-6 may be a mediator in the association between DII and birth weight. CONCLUSION: The diet of pregnant women may change the serum level of IL6, and then affect infant birth weight.

Characterisation of IL-15 and IL-2Rß in grass carp: IL-15 upregulates cytokines and transcription factors of type 1 immune response and NK cell activation.

Interleukin (IL) -15 belongs to the common cytokine receptor γ chain (γC) family and has diverse functions in regulating the development, proliferation and activation of NK and T cells. It activates a hetero-trimeric receptor complex consisting of IL-2Rα, IL-2Rß and a common γ chain (γC). In this study, the full-length cDNA sequences of IL-15 and IL-2Rß were identified in grass carp (Ctenopharyngodon idella, Ci) and their expression profiles analysed. The CiIL-15 and CiIL-2Rß were shown to be broadly expressed in tissues, with the highest levels detected in the spleen. Moreover, the CiIL-15 and CiIL-2Rß were modulated in primary head kidney leucocytes (HKLs) and splenocytes by immunostimulants and cytokines, and in the head kidney and spleen of fish after infection of Flavobacterium columnare and grass carp reovirus. The bioactivity of bacteria derived recombinant CiIL-15 protein was evaluated in the primary leucocytes. The CiIL-15 was shown to induce signature genes of type 1 immune response (IFN-γ and T-bet) and NK cell activation (perforin and Eomesa), whilst exhibiting inhibitory effects on the genes involved in the type 2 immune response (IL-4/13, IL-10 and Gata3). Our data suggest that IL-15 is a key regulator in promoting the type 1 immune response and NK cell activation in fish.