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Inflammatory signals direct expression of human IL12RB1 into multiple distinct isoforms. J Immunol 2012 Nov 01;189(9):4684-94

Date

10/02/2012

Pubmed ID

23024274

DOI

10.4049/jimmunol.1200606

Scopus ID

2-s2.0-84867909487   13 Citations

Abstract

IL12RB1 is essential for human resistance to multiple intracellular pathogens, including Mycobacterium tuberculosis. In its absence, the proinflammatory effects of the extracellular cytokines IL-12 and IL-23 fail to occur, and intracellular bacterial growth goes unchecked. Given the recent observation that mouse leukocytes express more than one isoform from il12rb1, we examined whether primary human leukocytes similarly express more than one isoform from IL12RB1. We observed that human leukocytes express as many as 13 distinct isoforms, the relative levels of each being driven by inflammatory stimuli both in vitro and in vivo. Surprisingly, the most abundant isoform present before stimulation is a heretofore uncharacterized intracellular form of the IL-12R (termed "isoform 2") that presumably has limited contact with extracellular cytokine. After stimulation, primary PBMCs, including the CD4(+), CD8(+), and CD56(+) lineages contained therein, alter the splicing of IL12RB1 RNA to increase the relative abundance of isoform 1, which confers IL-12/IL-23 responsiveness. These data demonstrate both a posttranscriptional mechanism by which cells regulate their IL-12/IL-23 responsiveness, and that leukocytes primarily express IL12RB1 in an intracellular form located away from extracellular cytokine.

Author List

Ford NR, Miller HE, Reeme AE, Waukau J, Bengtson C, Routes JM, Robinson RT

Authors

Christine E. Bengtson RN Nurse Practitioner in the Pediatrics department at Medical College of Wisconsin
Allison Reeme in the CTSI department at Medical College of Wisconsin - CTSI




MESH terms used to index this publication - Major topics in bold

Adult
Alternative Splicing
Amino Acid Sequence
Base Sequence
Chromosomes, Human, Pair 19
Exons
Gene Expression Regulation
Genome, Human
HEK293 Cells
Humans
Inflammation Mediators
Jurkat Cells
Molecular Sequence Data
Protein Isoforms
RNA Processing, Post-Transcriptional
Receptors, Interleukin-12
Signal Transduction