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Wnt5a–Rac1–NF-kB Homeostatic Circuitry Sustains Innate Immune Functions in Macrophages

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Wnt5a–Rac1–NF-kB Homeostatic Circuitry Sustains Innate Immune Functions in Macrophages
 
Creator Naskar, Debdut
Maiti, George
Chakraborty, Arijit
Roy, Arunava
Chattopadhyay, Dhrubajyoti
Sen, Malini
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description Macrophages play a critical role in innate immunity. Differentiation Ags present on macrophages such as CD14 orchestrate the first line of defense against infection. The basal/homeostatic signaling scheme that keeps macrophages thus groomed for innate immune functions remains unresolved. Wnt5a–Fz5 signaling being a primordial event during cell differentiation, we examined the involvement of Wnt5a–Fz5 signaling in the maintenance of innate immune functions. In this study, we demonstrate that innate immune functions of macrophages ensue at least partly through a homeostatic Wnt5a–Fz5–NF-kB (p65) circuit, which is Rac1 dependent. The autocrine/paracrine Wnt5a–Fz5–Rac1–p65 signaling cascade not only maintains basal levels of the immune defense modulating IFNs and CD14; it also supports macrophage survival. Wnt5a–Fz5–Rac1 signaling mediated p65 homeostasis in turn sustains Wnt5a expression in a feed-forward mode. The natural immune response of macrophages to Escherichia coli/LPS and virus is accordingly sustained. The depiction of sustenance of innate immune functions as an outcome of a homeostatic Wnt5a–p65 axis unfolds previously unidentified details of immune regulation and provides new insight into homeostatic cell signaling.
 
Publisher American Association of Immunologists
 
Date 2014
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2042/1/JOURNAL_OF_IMMUNOLOGY___192__(_9)_4386%2D4397_;2014[24].pdf
Naskar, Debdut and Maiti, George and Chakraborty, Arijit and Roy, Arunava and Chattopadhyay, Dhrubajyoti and Sen, Malini (2014) Wnt5a–Rac1–NF-kB Homeostatic Circuitry Sustains Innate Immune Functions in Macrophages. The Journal of Immunology, 192 (9). pp. 4386-4397. ISSN 0022-1767
 
Relation http://dx.doi.org/10.4049/jimmunol.1302817
http://www.eprints.iicb.res.in/2042/