Rat Anti-Mouse CD1d (CD1.1) Monoclonal antibody, clone 19G11 Functional Grade

Invariant natural killer T (iNKT) cells recognize activating self and microbial lipids presented by CD1d. CD1d can also bind non-activating lipids, such as sphingomyelin. We hypothesized that these serve as endogenous regulators and investigated humans and mice deficient in acid sphingomyelinase (ASM), an enzyme that degrades sphingomyelin. We show that ASM absence in mice leads to diminished CD1d-restricted antigen presentation and iNKT cell selection in the thymus, resulting in decreased iNKT cell levels and resistance to iNKT cell-mediated inflammatory conditions. Defective antigen presentation and decreased iNKT cells are also observed in ASM-deficient humans with Niemann-Pick disease, and ASM activity in healthy humans correlates with iNKT cell phenotype. Pharmacological ASM administration facilitates antigen presentation and restores the levels of iNKT cells in ASM-deficient mice. Together, these results demonstrate that control of non-agonistic CD1d-associated lipids is critical for iNKT cell development and function in vivo and represents a tight link between cellular sphingolipid metabolism and immunity.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality. Recently, we identified a novel biomarker, canopy fibroblast growth factor signaling regulator 2 (CNPY2) isoform2, and subsequently investigated its expression and prognostic value in CRC patients. We initially generated CNPY2 isoform2 monoclonal antibodies and examined CNPY2 isoform2 expression in CRC cell lines and tissues using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry analyses. We found that CNPY2 isoform2 expression significantly increased in tumor cell lines and tissues compared with that in normal colon epithelial cells and tumor-adjacent normal tissues. Survival analysis indicated that patients with low CNPY2 isoform2 expression had poorer 5-year overall survival (OS) in both the training cohort (41.7% vs. 77.7%, P = 0.007) and validation cohort (47.1% vs. 78.8%, P = 0.002). In multivariable analysis, CNPY2 isoform2 was identified as a predictor of 5-year OS in both the training cohort [hazard ratio (HR) = 5.001; 95% confidence interval (CI) 2.156-11.598, P < 0.001) and validation cohort (HR = 2.443; 95% CI 1.197-4.983, P = 0.014). In conclusion, CNPY2 isoform2 represents as a novel and valuable prognostic indicator for CRC patients, while the oncologic function of CNPY2 requires further study.