Human Blood CD1c+ Dendritic Cells Promote Th1 and Th17 Effector Function in Memory CD4+ T Cells.

Ingrid M Leal Rojas,Kristen J Radford,Yoshihito Minoda,Wai-Hong Mok,Ross T Barnard,Tony J Kenna,Frances E Pearson

doi:10.3389/fimmu.2017.00971

Abstract

Dendritic cells (DC) initiate the differentiation of CD4+ helper T cells into effector cells including Th1 and Th17 responses that play an important role in inflammation and autoimmune disease pathogenesis. In mice, Th1 and Th17 responses are regulated by different conventional (c) DC subsets, with cDC1 being the main producers of IL-12p70 and inducers of Th1 responses, while cDC2 produce IL-23 to promote Th17 responses. The role that human DC subsets play in memory CD4+ T cell activation is not known. This study investigated production of Th1 promoting cytokine IL-12p70, and Th17 promoting cytokines, IL-1β, IL-6, and IL-23, by human blood monocytes, CD1c+ DC, CD141+ DC, and plasmacytoid DC and examined their ability to induce Th1 and Th17 responses in memory CD4+ T cells. Human CD1c+ DC produced IL-12p70, IL-1β, IL-6, and IL-23 in response to R848 combined with LPS or poly I:C. CD141+ DC were also capable of producing IL-12p70 and IL-23 but were not as proficient as CD1c+ DC. Activated CD1c+ DC were endowed with the capacity to promote both Th1 and Th17 effector function in memory CD4+ T cells, characterized by high production of interferon-γ, IL-17A, IL-17F, IL-21, and IL-22. These findings support a role for CD1c+ DC in autoimmune inflammation where Th1/Th17 responses play an important role in disease pathogenesis.

Highlights

Dendritic cells (DC) are a heterogeneous population of leukocytes with specialized subsets responsible for driving specific immune responses [1,2,3]
CD141+ DC expressed the highest levels of TLR3 and comparable levels of TLR8 and IFIH1 to CD1c+ DC while TLR4, TLR7, and DDX58 were below the detection threshold. plasmacytoid DC (pDC) expressed the highest levels of TLR7 and weakly expressed IFIH1 while TLR3, TLR4, TLR8, DDX58, and IFIH1 were below the detection threshold (Figure 1)
This study investigated the ability of human blood DC subsets to promote Th1 and Th17 responses in memory CD4+ T cells

Summary

Introduction

Dendritic cells (DC) are a heterogeneous population of leukocytes with specialized subsets responsible for driving specific immune responses [1,2,3]. CDC1 require FLT3L and transcription factors IRF8, ID2, and Batf for their development and share expression of chemokine receptor XCR1, the CLR Clec9A, nectin-like protein 2 (CADM1), and TLR3 across species. In mice, these DC are crucial for immunity to intracellular infections and cancer, owing to their ability to produce high levels of IL-12p70, induce T helper (Th)-1 responses, and cross-present exogenous antigen for priming of CD8+ cytolytic T cell responses (CTL) [1]. Mouse cDC2 play a key role in the induction of immune responses to extracellular pathogens, owing to their ability to produce IL-23 that promotes Th17 type responses [4,5,6,7,8]

Methods

Results

Conclusion