Increased TREM-2 Expression on Dendritic Cell Subsets and Th2 and Th17 Immune Response in Allergic Airway Inflammation
Monday, March 5, 2018
South Hall A2 (Convention Center)
Sannette C. Hall, Devendra K. Agrawal, PhD MBA FAAAAI
RATIONALE: We have previously shown that allergen exposure increases TREM-2 and CCR-7 expression on mature DCs in the lungs and lymph nodes. Here, we further examined the phenotype of DC subsets and determined the T-helper cell responses associated with increased TREM-2 expression in the lungs and lymph nodes of allergen-sensitized and -challenged mice.

METHODS: Female Balb/c mice were sensitized and challenged with ovalbumin (OVA) for a total of 20 days. PBS was used in the control group. Whole lungs and lymph nodes were collected, prepared for FACS analysis and quantification of mRNA transcripts of CD4+ cell cytokines.

RESULTS: In the lungs and lymph nodes of OVA-sensitized and challenged mice, TREM-2+ DCs from all three populations (CD11bhi, CD103+ and CD11b+CD103+) had higher expression of CD86 and CCR7 compared to their TREM-2-negative counterparts. Cells expressing CD103 had overall high CCR-7 expression whereas CD86 was high on the CD11bhi subset. In the FACS analyses, we observed increased expression of GATA-3 and RORγt, increased mRNA transcripts of IL-4, IL-6, and IL-17 (p <0.01) and a decreased expression of T-bet and FoxP3 in both lungs and lymph nodes of OVA-sensitized and challenged mice.

CONCLUSIONS: These results suggest that increased TREM-2 expression on DCs in the lungs and lymph nodes is associated with Th2 and Th17 responses. Increased expression of CD86 and CCR7 on these cells highlights a potential role of TREM-2 in driving migration and/or maturation of DC subsets. Thus, TREM-2 could be an effective target for therapeutic intervention.