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Role of Wnt5a-Fz5 Signaling In Innate Immunity

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Title Role of Wnt5a-Fz5 Signaling In Innate Immunity
 
Creator Naskar, Debdut
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description Innate immunity provides the first line of defense against infection from various microorganisms. Among the different types of cells involved in innate immunity, macrophages play a very significant role. The presence of differentiation antigen such as CD14 on of macrophage surface is an important feature of macrophage mediated immune functions. How macrophages remain in such groomed condition in our system to counter infections remains an enigmatic question. The signaling pathways of homeostatic circuitry that keeps macrophages prepared to combat invasion remain unresolved. Although monocytic cells as well as macrophages harbor nuclear NFкB, it is unclear whether this nuclear NFκB engages in preparing macrophages for immune defense. I investigated (i) if a constitutive nuclear NFκB pool contributes to sustain macrophage mediated immune response and (ii) what cellular circuitry is responsible for such homeostasis. Because Wnt5a-Fz5 signaling is a primordial event during cell differentiation and has previously been shown to be involved in inflammation and phagocytosis, I examined the involvement of Wnt5a-Fz5 signaling in the constitutive presence of nuclear NFκB (p65) as well as maintenance of innate immune functions in macrophages. I demonstrated that a homeostatic Rac1 dependent Wnt5a-Fz5-NFκB (p65) circuit is at least partly responsible for keeping macrophages prepared for immune response. The autocrine/paracrine Wnt5a-Fz5-Rac1-p65 signaling cascade not only maintains basal levels of the immune defense modulating cytokines/interferons and CD14, but also supports macrophage survival. This homeostatic circuit accordingly drives the natural immune response of macrophages to E. coli/LPS and virus. The depiction of a functional cytokine/interferon response both in vitro and in vivo as an outcome of a homeostatic Wnt5a-p65 axis unfolds previously unidentified details of immune regulation in macrophages. Additionally, I demonstrated that Wnt5a signalling also contributes to monocytes survival and differentiation into macrophages.
 
Date 2014
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2077/1/Thesis__of_Debdut_Naskar.pdf
Naskar, Debdut (2014) Role of Wnt5a-Fz5 Signaling In Innate Immunity. PhD thesis, Calcutta University.
 
Relation http://www.eprints.iicb.res.in/2077/