Engineered cell migration to lesions linked to autoimmune disease. Issue 4 (8th January 2018)

• Record Type: Journal Article
• Authors: Mosabbir, Abdullah Al; Qudrat, Anam; Truong, Kevin
• Is Part Of: Biotechnology and bioengineering. Volume 115:Issue 4(2018)
• Page Start: 1028
• Page End: 1036
• Publication Date: 2018-01-08
• Subjects: blebbing -- Ca2+ signaling -- GM‐CSF -- GM‐CSF receptor -- migration -- protein engineering -- synthetic biology; Biotechnology -- Periodicals; Bioengineering -- Periodicals; 660.6
• DOI: 10.1002/bit.26523
• Languages: English
• ISSNs: 0006-3592

Abstract

Abstract: The damaging and degenerative effects in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and Crohn's disease often manifests as the formation of lesions that feature a high local concentration of granulocyte–macrophage colony‐stimulating factor (GM‐CSF). GM‐CSF along with other pro‐inflammatory factors form a positive feedback loop that ultimately perpetuate the lesions. Hence, to engineer chemotaxis to GM‐CSF, we created a new chimeric GM‐CSF receptor alpha subunit (GMRchi) that was coupled with a previously engineered Ca 2+ ‐activated RhoA. When these proteins were expressed in mammalian cells, it allowed migration to chemical and cellular sources of GM‐CSF. As a possible therapeutic intervention, we further implemented the mechanism of cell–cell membrane fusion and subsequent death. Since the microenvironment of lesions is more than just GM‐CSF secretion, the further ability to recognize a combination of other features such as tissue markers will be needed for greater specificity. Nonetheless, this work represents a first step to enable cell‐based therapy of autoimmune lesions. Abstract : Autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and Crohn's disease often manifests as the formation of lesions that feature a high local concentration of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Using a protein engineering approach, we have engineered cellular chemotaxis towards the GM‐CSF cytokine as a tool to deliver therapeutic cells to the site of autoimmune lesions.