Differential expression of tetraspanin superfamily members in dendritic cell subsets.

Malou Zuidscherwoude,Alie Van Der Schaaf,Sonja I Buschow,Annemiek B Van Spriel,Kuntal Worah

doi:10.1371/journal.pone.0184317

Abstract

Dendritic cells (DCs), which are essential for initiating immune responses, are comprised of different subsets. Tetraspanins organize dendritic cell membranes by facilitating protein-protein interactions within the so called tetraspanin web. In this study we analyzed expression of the complete tetraspanin superfamily in primary murine (CD4+, CD8+, pDC) and human DC subsets (CD1c+, CD141+, pDC) at the transcriptome and proteome level. Different RNA and protein expression profiles for the tetraspanin genes across human and murine DC subsets were identified. Although RNA expression levels of CD37 and CD82 were not significantly different between human DC subsets, CD9 RNA was highly expressed in pDCs, while CD9 protein expression was lower. This indicates that relative RNA and protein expression levels are not always in agreement. Both murine CD8α+ DCs and its regarded human counterpart, CD141+ DCs, displayed relatively high protein levels of CD81. CD53 protein was highly expressed on human pDCs in contrast to the relatively low protein expression of most other tetraspanins. This study demonstrates that tetraspanins are differentially expressed by human and murine DC subsets which provides a valuable resource that will aid the understanding of tetraspanin function in DC biology.

Highlights

Dendritic cells (DCs) are highly specialized immune cells that can sense tumor and microbial antigens and initiate both cellular and humoral immune responses
From these files we were able to identify 32 different tetraspanins expressed by human DCs of which 6 were excluded from the analyses due to low expression levels (< 5 in 2-out-of3 donors) which prevented reliable assessment of differential expression between subsets
The expression profiles differed greatly between the tetraspanin genes: CD9, CD53, TSPAN1, TSPAN3, TSPAN13 and TSPAN31 were relatively high expressed in pDCs compared to CD1c+ DCs and CD141+ DCs, whereas the other tetraspanin genes displayed higher mRNA levels in mDC subsets compared to pDCs (CD63, CD151, TSPAN17)

Summary

Introduction

Dendritic cells (DCs) are highly specialized immune cells that can sense tumor and microbial antigens and initiate both cellular and humoral immune responses. The complexity of the DC network has expanded enormously in the last decade by the identification of multiple different DC subsets. These subsets have been characterized by ontogeny, anatomical location, phenotypical markers, gene expression programs, and functionality [1,2]. The remarkable heterogeneity in DC subtypes may underlie a broad variety in the type, strength and duration of immune responses that may lead to either immunity or tolerance.

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Conclusion