Journal
PLOS GENETICS
Volume 10, Issue 10, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1004683
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Funding
- Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI12C1638]
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The mechanism underlying immune system recognition of different types of pathogens has been extensively studied over the past few decades; however, the mechanism by which healthy self-tissue evades an attack by its own immune system is less well-understood. Here, we established an autoimmune model of melanotic mass formation in Drosophila by genetically disrupting the basement membrane. We found that the basement membrane endows otherwise susceptible target tissues with self-tolerance that prevents autoimmunity, and further demonstrated that laminin is a key component for both structural maintenance and the self-tolerance checkpoint function of the basement membrane. Moreover, we found that cell integrity, as determined by cell-cell interaction and apicobasal polarity, functions as a second discrete checkpoint. Target tissues became vulnerable to blood cell encapsulation and subsequent melanization only after loss of both the basement membrane and cell integrity.
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