New IL-15 receptor-α splicing variants identified in intestinal epithelial Caco-2 cells

Abstract

IL-15 is a pleiotropic cytokine related to IL-2 which acts at a broader level than its counterpart. It is presented through its specific high-affinity receptor, IL-15Ra. Both cytokine and receptor are tightly regulated at multiple levels and are widely distributed. Thus, deregulation of their expression leads to an inflammatory immune response. Variants of splicing of IL-15Ra have been described in immune and barrier cells; however, their presence has not been focused on intestinal epithelial cells. In this study, we describe five new alternative variants of splicing of IL-15Ra in Caco-2 cells. Four of them were expressed into proteins inside Caco-2 cells, but these were unable to bind IL-15 or to follow the secretory pathway. However, the expression of mRNA itself might be relevant to diseases such as celiac disease, inflammatory bowel disease or colorectal cancer.

Primary human colonic mucosal barrier crosstalk with super oxygen-sensitiveFaecalibacterium prausnitziiin continuous culture

“…Similarly, direct effects of IL-15 on colon epithelia are unclear; its production is associated with paracrine regulation of cell survival, 91 and the Caco-2 cell line shows activation of downstream signaling by IL-15 92 but human intestinal epithelia do not express functional IL-15 receptors, only splice variants unable to bind IL-15. 93 Upregulation of IL-18, a cytokine essential for gut barrier integrity, 94 is consistent with reported effects of butyrate on gut barrier function. 95 Overall, the pattern of changes between GuMI-FP and relative to GuMI-FP suggest improved homeostatic functions consistent with enhanced exposure to butyrate.…”

Crosstalk between alternative splicing and inflammatory bowel disease: Basic mechanisms, biotechnological progresses and future perspectives

“…For example, some newly reported molecules, such as caspase-associated recruitment domain 8 (CARD8), neurokinin-1 receptor (NK-1R), orosomucoid 1-like protein 3 (ORMDL3), protein tyrosine phosphatase non-receptor type 2 (PTPN2), IL-15 receptor alpha (IL-15Rα) are all positional and functional candidate genes for IBD, and variants of splicing of these genes have been addressed by numerous reports. [145][146][147][148][149] NK-1R, a principal receptor of pro-inflammatory neuropeptide substance P (SP), has been proved to play a vital role in rodent models of chronic colitis and in UC as well as CD patients. 150,151 In 2015, Gillespie et al first examined the truncated (tr-NK-1R) and full-length (fl-NK-1R) receptor expressions in colonic tissues from patients of quiescent colitis, highgrade dysplasia (HGD) and CAC.…”

“…In addition to the molecules mentioned above in which their potential regulatory mechanisms in the pathogenesis of IBD have been fully elucidated, there are still many well‐established positive or negative regulatory genes encoded by different variants but lacking of detailed elaborations for their possible pro‐ or anti‐inflammatory mechanisms. For example, some newly reported molecules, such as caspase‐associated recruitment domain 8 (CARD8), neurokinin‐1 receptor (NK‐1R), orosomucoid 1‐like protein 3 (ORMDL3), protein tyrosine phosphatase non‐receptor type 2 (PTPN2), IL‐15 receptor alpha (IL‐15Rα) are all positional and functional candidate genes for IBD, and variants of splicing of these genes have been addressed by numerous reports 145–149 . NK‐1R, a principal receptor of pro‐inflammatory neuropeptide substance P (SP), has been proved to play a vital role in rodent models of chronic colitis and in UC as well as CD patients 150,151 .…”

Reduced Serum Levels of Soluble Interleukin-15 Receptor α in Schizophrenia and Its Relationship to the Excited Phenotype

“…IL-15Rα is ubiquitously produced in the brain as well as other organs; it activates multiple intracellular kinases through a trimeric receptor complex consisting of its specific receptor IL-15Rα and co-receptors interleukin 2 receptor β and interleukin 2 receptor γ (32,35,36). Both IL-15 and IL-15Rα have multiple splice variants and exist in different subcellular compartments (37)(38)(39)(40), suggesting that IL-15 signaling exhibits vital functions in neurodevelopment. IL-15 also can signal through IL-15Rα in the absence of other members of the trimeric complex, suggesting that this particular monomeric signaling unit has specific functions (41).…”