Altered Inactivation of commensal LPS due to acyloxyacyl hydrolase deficiency in colonic dendritic cells impairs mucosal Th17 immunity

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIAID	IMMUNO-4

* FARE Award Winner

Authors

• B.M. Janelsins
• M. Lu
• S.K. Datta

Abstract

Interleukin-17-secreting CD4+ helper T cells (Th17 cells) are essential for host defense at mucosal surfaces, and dysregulation can result in autoimmunity. Exposure to microbial products, such as bacterial LPS, can affect the ability of dendritic cells (DCs) to polarize Th17 cells. Acyloxyacyl hydrolase (AOAH) is a mammalian enzyme expressed by antigen (Ag)-presenting cells that deacylates and thereby inactivates LPS in host tissues. We hypothesized that inactivation of intestinal microbiota-derived LPS by AOAH influences the ability of DCs to polarize Th17 cells. We found that LPS-containing microbiota augmented the differentiation of Ag-specific Th17 cells, and identified a colonic DC subset (CD103+CD11b+ALDH-) that uniquely expresses AOAH and polarizes Th17 cells. Aoah-/- colonic DCs produce less IL-6, resulting in diminished Ag-specific Th17 polarization. Oral administration of LPS led to reduced IL-6 production from Aoah-/- colonic DCs compared with Aoah+/+ counterparts, resulting in attenuated Ag-specific Th17 responses in the colon after mucosal immunization that could be rescued by systemic delivery of IL-6. These data identify the ability of AOAH to modulate microbiota signals that drive Th17 polarization, and suggest that host pathways to handle commensal LPS may be targeted to modulate Th17 responses in the context of inflammatory disorders or infection at mucosal surfaces.

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