Wnt Signaling in Immune Cell Regulation During Microbial Infection and Cancer

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Background

Wnt signaling regulates central aspects of tissue and organ morphogenesis during embryonic development, as well as, tissue repair and homeostasis in the adult. Cellular functions directed by Wnt signaling include cytoskeletal modulations, organelle dynamics and specific transcriptional programs that regulate cell growth, differentiation and migration. Thus, it is not surprising that this fundamental signalling pathway also orchestrates host interactions with pathogens and the microbiota that co-exist and evolve with the host. Wnt signaling plays an important role in host immunity, is exploited by pathogens for survival, and interplay between microbiota and Wnt signaling occurs during different stages of growth and differentiation.

Wnt ligands comprise a family of glycoproteins, which generate signals upon binding to 7-transmembrane-domain receptors of the Frizzled family, as well as to ROR1/ROR2 and RYK cell surface receptors. Together with co-receptors, these interactions initiate intracellular signaling cascades generally classified by their engagement of β-catenin-dependent (“canonical”) or β-catenin-independent (“non-canonical”) events. In reality, there are frequent overlaps between intermediates involved in β-catenin-dependent and -independent signaling. The nature and outcome of Wnt signaling is shaped by the stoichiometry and combination of functional Wnt receptors.

The immune surveillance arbitrated by Wnt proteins spans across different immune cell types and relates to different levels of signaling that are influenced by several factors including cytoskeletal modulations and phenotypic adaptation to cytokine milieus characterized by a balance between pro-inflammatory and tolerogenic signatures. Furthermore, Wnt signaling shapes the tumor microenvironment by regulating the cross-talk between tumor cells and tumor-infiltrating leukocytes. Although Wnt signaling is now recognized as an important regulator of immune responses, many gaps remain in our understanding of how Wnt signaling is involved in regulating interactions of immune cells with phylogenetically diverse microbes and tumors.

This Research Topic aims to provide a comprehensive overview of Wnt signaling as it relates to immune homeostasis and regulation during host responses to pathogens, commensals and tumors. Accordingly, we welcome the submission of both Reviews and Original Research articles related to the following topics:

I. Wnt signaling in immune cell homeostasis

I.1: Analysis of Wnt signaling pathways in relation to cytoskeletal dynamics, protein/lipid trafficking and organellar movements, that are conducive to immune cell polarity and migration.

I.2: Analysis of Wnt signaling in relation to modulation of immune regulatory gene transcription.

I.3: Regulation of immune regulatory cytokine responses associated with polarity and migration of immune cells.

II. Wnt signaling in the tumor microenvironment

II.1: Wnt signaling and cross-talk between cancer cells and tumor-associated leukocytes.

II.2: Pro- and anti-tumor immune effects of Wnt signaling.

III. Wnt signaling in innate and adaptive immune responses to pathogens

III.1: Pathogen exploitation of Wnt signaling to manipulate host cell innate defenses, and host response to pathogens (e.g. phagocytosis, xenophagy, anti-microbial defenses by immune cells).

III.2: Orchestration of inflammation and the interplay between innate and adaptive immune responses.

III.3: Nature of Wnt immune responses as defined by microbial pathogenicity.

IV. Interplay between Wnt signaling and host microbiota

IV.1: Wnt protein-driven microbiome composition as a determinant of immune surveillance and host defense.

Keywords: Wnt signaling, Pathogen, Microbiota, Tumor, Immunity

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