Murine IL-4Δ2 splice variant down-regulates IL-4 activities independently of IL-4Rα binding and STAT-6 phosphorylation

Diogo, Gil R.; Sparrow, Adam; Paul, Mathew; Copland, Alastair; Hart, P. John; Stelter, Szymon; Dolleweerd, Craig J. van; Drake, Pascal M. W.; Macallan, Derek C.; Reljić, Rajko

doi:10.1016/j.cyto.2017.09.007

Cited by 3 publications

(1 citation statement)

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“…Unlike il-5, the δ2 isoform has been described previously for human [29] and mouse [30] Th2-cytokine IL-4. This IL-4δ2 form has a certain similarity to IL-5δ2; both have a deletion of the second exon (16 and 11 amino acids, respectively) and the overall architectural similarity with a four-helix bundle motif [31].…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel splice variant for mouse and human interleukin-5

Shilovskiy

Andreev

Mazurov

et al. 2020

Heliyon

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Expression of interleukins and their receptors is often regulated by alternative splicing. Alternative isoform of IL-5 receptor α-chain is well studied; however, no data on functional alternative splice variants of IL-5 has been reported up today. In the present study, we describe a novel splice variant for the mouse and human IL-5. The new form was found during analysis of PCR-products amplified from different mouse lymphoid tissues with a pair of primers designed to clone full-length mIL-5 ORF. A single short isoform of mIL-5 was detected along with the canonical full-length mRNA in ConA-stimulated lymphoid cells isolated from spleen, thymus, lymph nodes and blood. It was 30-40 nt shorter, and less abundant than classical form. The sequence analysis of an additional form of mIL-5 revealed that it lacks exon-2 (δ2). Using RT-PCR with the splice-specific primers we obtained an additional evidence for δ2 form expression. To verify whether mIL-5δ2 transcript is translated into protein, the coding sequences corresponding to full and δ2 forms of mIL-5 were cloned into an expression plasmid. After transfection into the human 293T cell line, we found that the short form of mIL-5 protein is expressed in cells and secreted into the supernatant, but at the reduced level than that detected for full isoform of mIL-5. Fluorescence microscopy examination revealed a partial translocation of mIL-5δ2 into cytoplasm, whereas mIL-5 resided mostly within endoplasmic reticulum. This can explain why the level of δ2 protein expression was reduced. Using a similar set of experimental approaches, we received the evidence that the human IL-5 mRNA has the δ2 splice form (hIL-5δ2) as well. It can be firmly detected by RT-PCR in PHA-activated mononuclear cells isolated from peripheral blood of healthy persons or patients with asthma. Altogether, our results showed that the human and mouse IL-5 have an alternative mRNA splice isoform, which loses exon-2, but nevertheless is expressed at protein level. However, more comprehensive studies will be required for evaluation of IL-5δ2 expression, regulation, biological function and clinical significance.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel splice variant for mouse and human interleukin-5

Shilovskiy

Andreev

Mazurov

et al. 2020

Heliyon

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Interleukin-4 signalling pathway underlies the anxiolytic effect induced by 3-deoxyadenosine

Gao

Hou

et al. 2019

Psychopharmacology

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Theoretical Studies of DNA Microarray Present Potential Molecular and Cellular Interconnectivity of Signaling Pathways in Immune System Dysregulation

Garcia,

Tayo

2024

Genes

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Autoimmunity is defined as the inability to regulate immunological activities in the body, especially in response to external triggers, leading to the attack of the tissues and organs of the host. Outcomes include the onset of autoimmune diseases whose effects are primarily due to dysregulated immune responses. In past years, there have been cases that show an increased susceptibility to other autoimmune disorders in patients who are already experiencing the same type of disease. Research in this field has started analyzing the potential molecular and cellular causes of this interconnectedness, bearing in mind the possibility of advancing drugs and therapies for the treatment of autoimmunity. With that, this study aimed to determine the correlation of four autoimmune diseases, which are type 1 diabetes (T1D), psoriasis (PSR), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE), by identifying highly preserved co-expressed genes among datasets using WGCNA. Functional annotation was then employed to characterize these sets of genes based on their systemic relationship as a whole to elucidate the biological processes, cellular components, and molecular functions of the pathways they are involved in. Lastly, drug repurposing analysis was performed to screen candidate drugs for repositioning that could regulate the abnormal expression of genes among the diseases. A total of thirteen modules were obtained from the analysis, the majority of which were associated with transcriptional, post-transcriptional, and post-translational modification processes. Also, the evaluation based on KEGG suggested the possible role of TH17 differentiation in the simultaneous onset of the four diseases. Furthermore, clomiphene was the top drug candidate for regulating overexpressed hub genes; meanwhile, prilocaine was the top drug for regulating under-expressed hub genes. This study was geared towards utilizing transcriptomics approaches for the assessment of microarray data, which is different from the use of traditional genomic analyses. Such a research design for investigating correlations among autoimmune diseases may be the first of its kind.

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Murine IL-4Δ2 splice variant down-regulates IL-4 activities independently of IL-4Rα binding and STAT-6 phosphorylation

Cited by 3 publications

References 50 publications

Identification of a novel splice variant for mouse and human interleukin-5

Identification of a novel splice variant for mouse and human interleukin-5

Interleukin-4 signalling pathway underlies the anxiolytic effect induced by 3-deoxyadenosine

Theoretical Studies of DNA Microarray Present Potential Molecular and Cellular Interconnectivity of Signaling Pathways in Immune System Dysregulation

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