rag1

Chemotherapy and radiotherapy frequently lead to intestinal damage. The mechanisms governing the repair or regeneration of intestinal damage are still not fully elucidated. Intraepithelial lymphocytes (IELs) are the primary immune cells residing in the intestinal epithelial layer. However, whether IELs are involved in intestinal epithelial injury repair remains unclear. Here, we found that IELs rapidly infiltrated the intestinal crypt region and are crucial for the recovery of the intestinal epithelium post-chemotherapy...

T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on patient prognosis remains challenging. In this study, we conducted comprehensive RNA sequencing in a cohort of 35 patients with T-ALL to unravel the intricate transcriptomic profile. Subsequently, we validated the prognostic relevance of 23 targets, encompassing (i) protein-coding genes- BAALC , HHEX , MEF2C , FAT1 , LYL1 , LMO2 , LYN , and TAL1 ; (ii) epigenetic modifiers- DOT1L , EP300 , EML4 , RAG1 , EZH2 , and KDM6A ; and (iii) long noncoding RNAs (lncRNAs)- XIST , PCAT18 , PCAT14 , LINC00202 , LINC00461 , LINC00648 , ST20 , MEF2C-AS1 , and MALAT1 in an independent cohort of 99 patients with T-ALL...

Recombination activating genes ( RAGs ) are tightly regulated during lymphoid differentiation, and their mutations cause a spectrum of severe immunological disorders. Hematopoietic stem and progenitor cell (HSPC) transplantation is the treatment of choice but is limited by donor availability and toxicity. To overcome these issues, we developed gene editing strategies targeting a corrective sequence into the human RAG1 gene by homology-directed repair (HDR) and validated them by tailored two-dimensional, three-dimensional, and in vivo xenotransplant platforms to assess rescue of expression and function...

Toxin- and drug-induced tubulointerstitial nephritis (TIN), characterized by interstitial infiltration of immune cells, frequently necessitates dialysis for patients due to irreversible fibrosis. However, agents modulating interstitial immune cells are lacking. Here, we addressed whether the housekeeping enzyme glutamyl-prolyl-transfer RNA synthetase 1 (EPRS1), responsible for attaching glutamic acid and proline to transfer RNA, modulates immune cell activity during TIN and whether its pharmacological inhibition abrogates fibrotic transformation...

Guigarracailaoensis is a member of family Cyprinidae, subfamily Labeoninae (Cypriniformes) which was recently discovered in southwestern China. Following its initial description, additional information on this species has remained notably scarce. In the current study, we assemble the complete mitochondrial genome (mitogenome) of G.cailaoensis using the Illumina sequencing platform. The mitogenome is identified as a circular, double-stranded DNA sequence of 16,593 base pairs, encompassing 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and a putative control region...

BACKGROUND: It is well-established that CD8+ T-cells play a critical role in graft rejection. The basic leucine zipper ATF-like transcription factor (BATF) and BATF3 are transcriptional factors expressed in T lymphocytes. Herein, we investigated the functions of BATF and BATF3 in the differentiation and exhaustion of CD8+ T cells following alloantigen activation. METHODS: Wild-type CD8+ T cells, BATF-deficient (Batf-/- ) CD8+ T cells, and CD8+ T cells deficient in both BATF and BATF3 (Batf-/- Batf3-/- ) were transferred to B6...

UNLABELLED: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions. Despite their potential for adoptive cell therapy, studies into their anti-cancer activity, including their role in colon cancer, are limited. We expanded MAIT cells in vivo and injected them into RAG1 -/- mice with MC38-derived tumors and tumor growth was assessed...

Patients with sepsis always have a high mortality rate, and acute kidney injury (AKI) is the main cause of death. It seems obvious that the immune response is involved in this process, but the specific mechanism is unknown, especially the pathogenic role of T cells and B cells needs to be further clarified. Acute kidney injury models induced by lipopolysaccharide were established using T-cell, B-cell, and T&B cell knockout mice to elucidate the role of immune cells in sepsis. Flow cytometry was used to validate the mouse models, and the pathology can confirm renal tubular injury...

Balancing selection is the process of selection that preserves various alleles within a population. Studying the areas undergoing balancing selection is essential, because it preserves genetic diversity in a population. Finding genes that exhibit signs of balancing selection during the domestication of cattle is the goal of this study. To identify regions where polymorphism has persisted in the cattle population for millions of years, we examined the genome of cattle. In this study, we used bovine SNP 50 k data to conduct a detailed genome-wide assessment of selection signatures for balancing selection...

BACKGROUND: As hybridization can reduce biodiversity or cause extinction, it is important to identify both purebred parental species and their hybrids prior to conserving them. The Suwon tree frog, Dryophytes suweonensis, is an endangered wildlife species in Korea that shares its habitat and often hybridizes with the Japanese tree frog, D. japonicus . In particular, D. suweonensis , D. japonicus , and their hybrids often have abnormal ovaries and gonads, which are known causes that could threaten their existence...

Recombination-activating gene 1 (RAG1) is a vital player in V(D)J recombination, a fundamental process in primary B cell and T cell receptor diversification of the adaptive immune system. Current vertebrate RAG evolved from RAG transposon; however, it has been modified to play a crucial role in the adaptive system instead of being irreversibly silenced by CpG methylation. By interrogating a range of publicly available datasets, the current study investigated whether RAG1 has retained a disproportionate level of its original CpG dinucleotides compared to other genes, thereby rendering it more exposed to methylation-mediated mutation...

BACKGROUND: The Asian leaf litter toads of the genus Leptobrachella Smith, 1925 (Anura, Megophryidae) inhabit the forest floor and rocky streams in hilly evergreen forests and are widely distributed from southern China, west to north-eastern India and Myanmar, through mainland Indochina to Peninsular Malaysia and the Island of Borneo. NEW INFORMATION: A new species of the Asian leaf litter toad genus Leptobrachella from Guizhou Province, China is described. Molecular phylogenetic analyses, based on mitochondrial 16S rRNA and COI genes and nuclear RAG1 gene sequences indicated that the new species is genetically divergent from its congeners...

The landscape of chromosomal aberrations in the tumor cells of the patients with B-ALL is diverse and can influence the outcome of the disease. Molecular karyotyping at the onset of the disease using chromosomal microarray (CMA) is advisable to identify additional molecular factors associated with the prognosis of the disease. Molecular karyotyping data for 36 patients with Ph-negative B-ALL who received therapy according to the ALL-2016 protocol are presented. We analyzed copy number alterations and their prognostic significance for CDKN2A / B , DMRTA , DOCK8 , TP53 , SMARCA2 , PAX5 , XPA , FOXE1 , HEMGN , USP45 , RUNX1 , NF1 , IGF2BP1 , ERG , TMPRSS2 , CRLF2 , FGFR3 , FLNB , IKZF1 , RUNX2 , ARID1B , CIP2A , PIK3CA , ATM , RB1 , BIRC3 , MYC , IKZF3 , ETV6 , ZNF384 , PTPRJ , CCL20 , PAX3 , MTCH2 , TCF3 , IKZF2 , BTG1 , BTG2 , RAG1 , RAG2 , ELK3 , SH2B3 , EP300 , MAP2K2 , EBI3 , MEF2D , MEF2C , CEBPA , and TBLXR1 genes, choosing t(4;11) and t(7;14) as reference events...

CD247, also known as CD3ζ, is a crucial signaling molecule that transduces signals delivered by TCR through its three ITAMs. CD3ζ is required for successful thymocyte development. Three additional alternatively spliced variants of murine CD247 have been described, that is, CD3ι, CD3θ, and CD3η, that differ from CD3ζ in the C terminus such that the third ITAM is lost. Previous studies demonstrated defects in T cell development in mice expressing CD3η, but the TCR signaling pathways affected by CD3η and the impacts of the CD3ι and CD3θ on T cell development were not explored...

Asian shrew moles, genus Uropsilus , are the most primitive members of family Talpidae. They are distributed mainly in southwestern China and adjacent Bhutan, Myanmar, and Vietnam. In June 2022, we collected five specimens of Uropsilus from Mount Huanggang, Jiangxi Province, eastern China, which is the highest peak of the Wuyi Mountains. We sequenced two mitochondrial ( CYT B and 12S rRNA ) and three nuclear ( PLCB4 , RAG1 , and RAG2 ) genes to estimate the phylogenetic relationship of the five shrew moles...

Viral vectors are being used for the treatment of cancer. Yet their efficacy varies among tumors and their use poses challenges in immunosuppressed patients, underscoring the need for alternatives. We report striking antitumoral effects by a nonlytic viral vector based on attenuated lymphocytic choriomeningitis virus (r3LCMV). We show in multiple tumor models that injection of tumor-bearing mice with this novel vector results in improved tumor control and survival. Importantly, r3LCMV also improved tumor control in immunodeficient Rag1-/- mice...

Recombination-activating genes (RAG1 and RAG2) are critical in lymphoid cell development and function by initiating the V(D)J-recombination process to generate polyclonal lymphocytes with broad antigen-specificity. Clinical manifestations of defective RAG1/2 genes range from immune dysregulation to severe combined immunodeficiencies (SCID), causing life-threatening infections and death early in life without hematopoietic cell transplantation (HCT). Despite improvements, haploidentical HCT without myeloablative conditioning carries a high risk of graft failure and incomplete immune reconstitution...

Four strains of experimentally naïve mice (NOD. Cg- Prkdc scid Il2rg tm1Wjl /SzJ [NSG], NOD. Cg- Rag1 tm1Mom Il2rg tm1Wjl /SzJ [NRG], B6.129S(Cg)- Stat1 tm1Dlv /J [STAT1 -/- ], and B6.129S7- Ifngr1 tm1Agt /J[IFNγR -/- ] housed in a barrier facility developed unusual and seemingly unrelated clinical signs. Young NSG/NRG mice ( n = 49, mean age = 4 ± 0.4 mo) exhibited nonspecific clinical signs of moderate-to-severe lethargy, hunched posture, decreased body condition, and pallor. In contrast to the NSG/NRG mice, the STAT1-/- and IFNγ R-/- mice ( n = 5) developed large subcutaneous abscesses on the head and neck...

The stringent regulation of RAGs (Recombination activating genes), the site-specific endonuclease responsible for V(D)J recombination, is important to prevent genomic rearrangements and chromosomal translocations in lymphoid cells. In the present study, we identify a microRNA, miR-501, which can regulate the expression of RAG1 in lymphoid cells. Overexpression of the pre-miRNA construct led to the generation of mature miRNAs and a concomitant reduction of RAG1 expression, whereas inhibition using anti-miRs resulted in its enhanced expression...

Vaccination of farmed fish is the most effective prophylactic measure against contagious diseases but requires specific knowledge on when the adaptive immune system is fully developed. The present work describes kidney and spleen morphogenesis as well as B-cell development in the ballan wrasse (Labrus bergylta). The kidney was present at hatching (0 days pot hatching, dph) but was not lymphoid before larvae was 50-60 dph (stage 5), containing abundant Igμ+ cells. The spleen anlage was first observed in larvae at 20-30 dph and was later populated with B-cells...