Interleukin-12p40 variant form reduces Interleukin-12p80 secretion

•An IL-12p40 variant form was discovered.•The Il12b variant is expressed in activated BMDCs and some lymphoid tissues.•The IL-12p40 variant form suppresses the formation and secretion of IL-12p80. IL-12 is a key cytokine for the promotion of CD4+ T cells differentiation to type 1 helper T cells. IL-...

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Bibliographic Details
Published in:	Cytokine (Philadelphia, Pa.) Vol. 120; pp. 251 - 257
Main Authors:	Oshikiri, Yumi, Nara, Hidetoshi, Takeda, Yuji, Araki, Akemi, Nemoto, Nobuhito, Gazi, Md. Yeashin, Saito, Shoko, Saitoh, Shinichi, Nakajima, Osamu, Asao, Hironobu
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-08-2019
Subjects:	IL-12p40 IL-12p80 Interleukin-12 Splice variant Splice variant IFN-γ IL-12p40 BMDC Interleukin-12 IL-12p80 IL-12 LPS
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Summary:	•An IL-12p40 variant form was discovered.•The Il12b variant is expressed in activated BMDCs and some lymphoid tissues.•The IL-12p40 variant form suppresses the formation and secretion of IL-12p80. IL-12 is a key cytokine for the promotion of CD4+ T cells differentiation to type 1 helper T cells. IL-12 is a heterodimer (IL-12p70) consisting of p40 and p35 subunits, and is mainly secreted from activated antigen-presenting cells, such as macrophages and dendritic cells (DCs). In this study, we found that activated mouse bone marrow-derived DCs (BMDCs) produced a p40 splice variant form mRNA in addition to the conventional p40 mRNA. This p40 variant mRNA was produced by alternative splicing in exon 5, and possessed a premature stop codon. As a result, the p40 variant protein contained 157 amino acids of the N-terminal part of p40 and an additional 10 novel amino acids. When the p40 variant was expressed in HEK-293T cells, it was not secreted from the cells. To investigate the function of the p40 variant, it was co-expressed with p40 and/or p35. The p40 variant did not affect the secretion of IL-12p40 or IL-12p70, or the function of the secreted p70. In contrast, the secretion of IL-12p80, a homodimeric IL-12 with two p40 subunits, was significantly decreased when the p40 variant was expressed. This new splicing variant p40 may act to fine-tune the function of IL-12p80.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1043-4666 1096-0023
DOI:	10.1016/j.cyto.2019.05.017