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Review
. 2016 Mar;7(3):159-74.
doi: 10.1007/s13238-016-0250-0. Epub 2016 Mar 2.

Role of Notch signaling in regulating innate immunity and inflammation in health and disease

Yingli Shang  1 , Sinead Smith  2 , Xiaoyu Hu  3
Affiliations
Review

Role of Notch signaling in regulating innate immunity and inflammation in health and disease

Yingli Shang et al. Protein Cell. 2016 Mar.

Abstract

The Notch signaling pathway is conserved from Drosophila to mammals and is critically involved in developmental processes. In the immune system, it has been established that Notch signaling regulates multiple steps of T and B cell development in both central and peripheral lymphoid organs. Relative to the well documented role of Notch signaling in lymphocyte development, less is known about its role in regulating myeloid lineage development and function, especially in the context of acute and chronic inflammation. In this review article, we will describe the evidence accumulated during the recent years to support a key regulatory role of the Notch pathway in innate immune and inflammatory responses and discuss the potential implications of such regulation for pathogenesis and therapy of inflammatory disorders.

Keywords: Notch signaling; RBP-J; inflammation; innate immunity; macrophages.

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Figures

Figure 1
Figure 1
A model for activation of Notch target gene expression in human macrophages. Both signal 1 and signal 2 are required to achieve full-fledged induction of Notch target genes by stimuli such as TLR ligands. Signal 1 is provided by constitutive tonic Notch signaling in macrophages presumably as a result of macrophage-macrophage or macrophage-stromal cell interaction. Signal 2 is provided by TLR stimulation in the form of p38-mediated phosphorylation of histones at the Notch target gene loci
Figure 2
Figure 2
Regulation of myeloid cell development and differentiation by Notch signaling. Notch signaling critically controls multiple steps of myeloid cell development and differentiation program including early myelopoiesis, development of certain DC population, osteoclast differentiation, and inflammatory macrophage polarization. Abbreviations: HSC, hematopoietic stem cell; GMP, granulocyte-macrophage progenitor; MDP, macrophage-dendritic cell progenitor; CDP, common dendritic cell precursor; OCP, osteoclast precursor; pDC, plasmacytoid dendritic cells
Figure 3
Figure 3
Crosstalk between the TLR signaling pathway and the Notch pathway. Expression and/or function of various components of the Notch pathways could be regulated by TLR signaling. Conversely, Notch pathway components positively or negatively modulate TLR-activated transcriptional, translational, and metabolic programs to finetune outcomes of immune responses
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