Slc3a2 exerts a tuning effect on mast cell function by selectively impacting the profile of stored mediators

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Presentation Time: 05:30 PM - 05:45 PM
Abstract ID: 5181 - B

Presenting Author:
Nyssa B Samanas , Research Scientist III at Seattle Children’s Hosp.

Abstract:

Solute carrier transporters (SLCs) are a large superfamily of proteins that have recently drawn investigative interest as potential drug targets. Slc3a2, the heavy chain of the amino acid transporter CD98, is expressed at a very high level in mast cells relative to other immune cells, but its role in mast cell function is presently unknown. We found that mouse mast cells lacking Slc3a2 have lower granularity and granule density accompanied by a decrease in granule acidification as well as less mature granule staining. Despite these profound alterations in granule loading and maturation, further proteomic and RNA-seq analyses demonstrated that only a subset of granule contents is affected by Slc3a2 deficiency. To determine how this alteration in granule composition translates to mast cell function in vivo, we tested the activity of mast cells in the skin of mice lacking Slc3a2 in connective tissue mast cells in both a passive cutaneous anaphylaxis model as well as an atopic dermatitis model. Interestingly, we found that mice with mast cells deficient in Slc3a2 showed an increased local inflammatory response in the anaphylaxis model but a decreased response in the atopic dermatitis model. This intriguing finding suggests that the loss of Slc3a2 may have a tuning effect on mast cells by altering the profile of specific stored mediators that differentially contribute to the development of mast cell-dependent responses.