ID: 179: ABIN1 inhibits IL-17 signaling in a feedback manner

• Published in: Cytokine (Philadelphia, Pa.) Vol. 76; no. 1; p. 97
• Main Authors: Agustin Cruz, J., Garg, Abhishek V., Amatya, Nilesh, Ma, Averil, Gaffen, Sarah L.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.11.2015
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2015.08.189

The Interleukin-17A (IL-17A) is related to the development of autoimmune diseases as well as to the control of Candida albicans infections. IL-17 triggers signaling by binding to the IL-17 receptor (IL-17R). The IL-17R recruits adaptor proteins activating downstream effector pathways such as NF-κB and MAPK to induce inflammatory gene expression. To identify IL-17 signaling intermediates we screened candidate genes by siRNA knockdown discovering several novel inhibitors. Based on evidence from human genetic studies and the known importance of A20 as an inhibitor of IL-17R signaling we focused on ABIN1, an A20-interacting protein, which has not previously implicated in this pathway. Since many inhibitors work in a feedback manner to block the pathways that induce their expression, we asked whether IL-17R signaling regulates expression of ABIN1. Indeed, mRNA expression of ABIN1 was induced by IL-17A signaling. Upon ABIN1 knockdown, the IL-17-dependent gene Lipocalin2 (Lcn2) showed increased expression, confirming that ABIN1 is an inhibitor of the IL-17R signaling. Consistently, reconstitution of ABIN1-deficient fibroblast with ABIN1 suppressed Lcn2 expression, and IL-17-induced activation of Lcn2 promoter was downregulated when ABIN1 was ectopically expressed in ST2 cells. However, not all IL-17-dependent target genes were regulated by ABIN1. We are currently dissecting the mechanisms by which ABIN1 inhibits IL-17R signaling. Together, these findings suggest an unexpected complexity in the regulation of IL-17-mediated inflammation.