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Dendritic Cell Differential Gene Expression Associated with the Irritant Versus Allergenic Effect of TMA Exposure
Sunday, March 6, 2016: 4:45 PM
Concourse Foyer (Convention Center)
Debajyoti Ghosh, PhD, Ian P. Lewkowich, PhD, Jonathan A Bernstein, M.D.
Rationale: Workplace exposure to Trimellitic Anhydride (TMA), can elicit either an irritant response caused by free TMA or an IgE-mediated immune response which can occur when TMA binds to endogenous proteins like human serum albumin (HSA) and in susceptible individuals results in sensitization and potentially occupational asthma. Dendritic cells (DC) are critical for processing environmental irritants and allergens but the molecular pathways through which DCs discriminate TMA-mediated irritant from IgE-immune responses are poorly characterized.

Methods: Human plasmacytoid DC (pDC) expressing FcER1+ were sensitized with TMA-IgE sensitized workers' sera  (n=2) at a 1:20 dilution, washed and exposed to either (a) HSA; (b) free TMA or; (c) an LPS-free TMA-HSA conjugate.  Cells were harvested and analyzed by RNA sequencing. Unexposed DCs or DCs incubated with non-TMA exposed control sera served as additional controls. Differentially expressed genes (DEGs; adjusted p-values <0.05) were used for bioinformatic analyses.

Results: Free TMA exposure associated-DEGs involved innate immunity and cell migration pathways including IL23A, IL15, epiregulin and endothelin.  In contrast, TMA-HSA exposure was associated with DEGs involved in humoral immune responses including SORBS1, TNFSF13B, CD300LB and LYN tyrosin kinase. Pathway analyses revealed over-representation of Granzyme B pathway genes and inflammatory immune genes for the free TMA and TMA-HSA groups, respectively. Specific cytokines (IL1, IL6) and chemokines (CCL4, CCL20) were upregulated in both groups.

Conclusions: Gene expression of pDCs exposed to free TMA is distinctly different from pDCs exposed to TMA-HSA. Real-time PCR studies are in progress to more precisely understand these findings.