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 Ca2+ -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.
journal_name
Biotechnol Bioengjournal_title
Biotechnology and bioengineeringauthors
Mosabbir AA,Qudrat A,Truong Kdoi
10.1002/bit.26523subject
Has Abstractpub_date
2018-04-01 00:00:00pages
1028-1036issue
4eissn
0006-3592issn
1097-0290journal_volume
115pub_type
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