Undergraduate Researcher Swarthmore Col., United States
Disclosure(s):
William Trone: No financial relationships to disclose
Introduction/Rationale: Erythroid cells, like classical immune cells, arise from hematopoietic stem cells, yet their immune potential remains largely unexplored.
Methods: To investigate their role in immunity, we analyzed single cell RNA-seq data from human umbilical cord blood and discovered that erythroid progenitors express key components of the cytosolic DNA-sensing cGAS-STING pathway. We confirmed constitutive expression and canonical localization of these genes in human umbilical cord blood-derived erythroid progenitor (HUDEP-2) cells.
Results: HUDEP-2 cells are a unique model to probe the DNA-sensing capacity of erythroid progenitors due to their doxycycline-inducible expression of HPV-E7, which degrades STING. Surprisingly, despite degradation of STING, HUDEP-2 cells mounted a robust transcriptional response to transfection with dsDNA. These changes did not align with a type I interferon response, but instead pointed to a non-canonical NFκB-dependent activation. Upregulated genes were enriched for immune cell differentiation pathways, including myeloid-specific transcription factors.
Conclusion: Our results suggest that erythroid progenitors are capable of sensing exogenous DNA independently of STING and subsequently initiating a non-canonical, interferon-independent immune program that may influence lineage fate decisions. These findings challenge the assumption that erythroid progenitors are immunologically inert and instead suggest a role for erythroid cells in mediating innate antiviral immunity and hematopoiesis.
