Identification of the Siglec-8-induced mode of eosinophil death and extracellular factors governing Siglec-6/8 expression and function

Project: Research project

Project Details

Description

Eosinophils and mast cells are critical immune effector cells in allergic disease. Through their inappropriate expansion, survival, recruitment, or activation, these cells contribute to anaphylaxis, asthma, chronic rhinosinusitis, eosinophilic gastrointestinal disorders (EGID), and atopic dermatitis, among other conditions. The cell-surface receptors Siglec-6 and Siglec-8 belong to the family of sialic acid-binding immunoglobulin-like lectins (siglecs) and, as siglecs bearing ITIM and ITIM-like cytoplasmic motifs, are expected to play inhibitory roles in the cells that express them. Siglec-6 is expressed by mast cells, placental trophoblasts, and some B cells whereas Siglec-8 is expressed by eosinophils, mast cells, and basophils. While we have established that Siglec-8 induces the cell death of cytokine-primed eosinophils, this mode of cell death has been described variously and has never been properly characterized, leaving open the critical questions of whether this cell death is pro- or non-inflammatory and what purpose it might serve physiologically. In addition, we have found evidence of modulation of Siglec-8 cell-surface levels and Siglec-8 function through nutrient levels and a nutrient-sensing pathway. How this occurs and whether Siglec-6 expression and function is regulated in the same manner will be explored within this project.
StatusFinished
Effective start/end date9/1/188/31/19

Funding

  • University of California, San Diego (107905120//3U19AI070535-12S1)
  • National Institute of Allergy and Infectious Diseases (107905120//3U19AI070535-12S1)

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