Human CD141+ Dendritic Cells Induce CD4+ T Cells To Produce Type 2 Cytokines

Abstract

Dendritic cells (DCs) play the central role in the priming of naïve T cells and the differentiation of unique effector T cells. Here, using lung tissues and blood from both humans and humanized mice, we analyzed the response of human CD1c+ and CD141+ DC subsets to live-attenuated influenza virus (LAIV). Specifically, we analyzed the type of CD4+ T cell immunity elicited by LAIV-exposed DCs. Both DC subsets induce proliferation of allogeneic naïve CD4+ T cells with capacity to secrete IFN-γ. However, CD141+ DCs are uniquely able to induce the differentiation of IL-4 and IL-13 producing CD4+ T cells. CD141+ DCs induce IL-4 and IL-13 secreting CD4+ T cells through OX40L. Thus, CD141+ DCs demonstrate remarkable plasticity in guiding adaptive immune responses.

Cigarette Smoke Extract Promotes TIM4 Expression in Murine Dendritic Cells Leading to Th2 Polarization through ERK-Dependent Pathways

“…Previous research reports that DCs express TIM4, and it plays an important role in inducing Th2 polarization [21]. However, the way on how to elevate TIM4 expression in DCs remains unknown.…”

Human dendritic cell subsets and function in health and disease

“…T cells, induce CD4 ? T cell proliferation and polarize Th1 responses [16,29,55]. However, in these studies, CD1c ?…”

“…DC subset in particular for immunotherapeutic vaccines for cancer [30,54]. [55], an observation that would not have been predicted from mouse studies, where the CD11b ? DC are more efficient in promoting Th2 responses.…”

Dendritic Cells in Human Lung Disease

“…House dust mite allergen upregulates CD141 expression on monocyte derived DC 27 . This is significant because CD141 expressing DC induce a strongly Th2-polarized cytokine response in naïve 28 and memory CD4 T-cells 27 , while CD141 expression in blood leukocytes is elevated during acute asthma exacerbations 27 .…”