Negative immune regulator TIPE2 promotes M2 macrophage differentiation through the activation of PI3K-AKT signaling pathway

13Citations
Citations of this article
13Readers
Mendeley users who have this article in their library.

Abstract

Macrophages play important roles in the regulation of the innate and adaptive immune responses. Classically activated macrophages and alternatively activated macrophages are the two major forms of macrophages and have opposing functionalities. Tumor necrosis factor-α-induced protein 8-2 is expressed primarily by immune cells and negatively regulates type 1 innate and adaptive immune responses to maintain immune tolerance. While previous studies indicate that TIPE2 promotes M2 but inhibits M1 macrophage differentiation, the underlying molecular mechanism by which TIPE2 promotes M2 macrophage differentiation remains unclear. Our current study shows that TIPE2-deficient bone-marrow cells are defective in IL-4 induced M2 macrophage differentiation in vitro. Mechanistic studies revealed that TIPE2 promotes phosphoinositide metabolism and the activation of the downstream AKT signaling pathway, which in turn leads to the expression of markers specific for M2 macrophages. In addition, our results showed that Tipe2-deficiency does not affect the activation of the JAK-STAT6 signaling pathway that also plays an important role during M2 macrophage differentiation. Taken together, these results indicate that TIPE2 promotes M2 macrophage differentiation through the activation of PI3K-AKT signaling pathway, and may play an important role during the resolution of inflammation, parasite control, as well as tissue repair.

Cite

CITATION STYLE

APA

Liu, R., Fan, T., Geng, W., Chen, Y. H., Ruan, Q., & Zhang, C. (2017). Negative immune regulator TIPE2 promotes M2 macrophage differentiation through the activation of PI3K-AKT signaling pathway. PLoS ONE, 12(1). https://doi.org/10.1371/journal.pone.0170666

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free