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Steroid Hormones and Immunity

Investigating the regulation of the Imd pathway led to the discovery that the steroid hormone 20-hydroxyecdysone (20E) provides systemic control to this immune response. 20E is best known for triggering major developmental transitions during the life-cycle of Drosophila and other insects. We have found that 20E also potently regulates the expression of the key PGN sensing receptor PGRP-LC. Through this regulatory interaction, the Imd response is developmentally regulated. We have further discovered that in adult flies 20E levels can fluctuate. In particular 20E rises with stresses like dehydration and leads to adaptive enhancement, or priming, of this innate immune response. Surprisingly, we have also found that some components of the Imd pathway, especially the NF-κB factor Relish, play key roles in regulating certain 20E-triggered, developmentally programmed events such as the degradation of the salivary gland via autophagic cell death during metamorphosis. This transcriptional regulation of autophagy is unusual and seems to involve a non-canonical use of some, but not all, of the Imd pathway components.