Notch signaling at the crossroads of innate and adaptive immunity

Abstract

Notch signaling is an evolutionarily conserved cell-to-cell signaling pathway that regulates cellular differentiation and function across multiple tissue types and developmental stages. In this review, we discuss our current understanding of Notch signaling in mammalian innate and adaptive immunity. The importance of Notch signaling is pervasive throughout the immune system, as it elicits lineage and context-dependent effects in a wide repertoire of cells. Although regulation of binary cell fate decisions encompasses many of the functions first ascribed to Notch in the immune system, recent advances in the field have refined and expanded our view of the Notch pathway beyond this initial concept. From establishing T cell identity in the thymus to regulating mature T cell function in the periphery, the Notch pathway is an essential, recurring signal for the T cell lineage. Among B cells, Notch signaling is required for the development and maintenance of marginal zone B cells in the spleen. Emerging roles for Notch signaling in innate and innate-like lineages such as classical dendritic cells and innate lymphoid cells are likewise coming into view. Lastly, we speculate on the molecular underpinnings that shape the activity and versatility of the Notch pathway.

Treponema denticola dentilisin triggered TLR2/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells

“…Several other pathways modulate TLR-signaling, fostering tissue-specific outcomes. Synergistic cooperation between the Notch pathway and acute TLR-induced signals in the activation of canonical and non-canonical Notch target genes has been characterized as an integral pathway governing the regulation of innate and adaptive immunity [115][116][117][118]. Consistent with this, our KEGG pathway analysis revealed Notch signaling (~2-fold change) as the second most enriched pathway resulting from T. denticola challenge in hPDL cells 22-hours post-challenge (Fig 1D).…”

Transcriptome Analysis of Crassostrea sikamea (♀) × Crassostrea gigas (♂) Hybrids Under Hypoxia in Occluded Water

“…In the previous studies, fibropellin-1, related to the Notch protein, drastically increased when post chronic hypoxia in the clam Ruditapes philippinarum (Nie et al, 2020) and the NOTCHs were upregulated in Hermodice carunculata under hypoxia (Grimes et al, 2021). Notch signaling was originally identified as a pleiotropic mediator of cell fate in invertebrates, which has recently emerged as an important regulator of immune cells (Radtke et al, 2013;Vanderbeck and Maillard, 2021). In the current study, several upregulated DEGs were annotated into the notch signaling pathway, which participates in the response to hypoxia stress by regulating the innate immunity in oyster gills.…”

Innate and Adaptive Immunity in Giant Cell Arteritis

“…NOTCH1 is an oncogene, most notably, NOTCH1 mutations are present in the majority of patients with T cell acute lymphocytic leukemia ( 71 ). NOTCH signaling controls cell fate decisions and is needed for the specification of T cells; directs cell proliferation, differentiation, and cell death ( 72 , 73 ). In GCA, NOTCH1 expression on circulating CD4 + T cells has been implicated in enabling their transition from the blood into the tissue, representing a major tolerance defect in this disease.…”