Abstract

This paper distinguishes a rare subset of myeloid dendritic-like cells found in mouse spleen from conventional (c) dendritic cells (DC) in terms of phenotype, function and gene expression. These cells are tentatively named “L-DC” since they resemble dendritic-like cells produced in longterm cultures of spleen. L-DC can be distinguished on the basis of their unique phenotype as CD11bhiCD11cloMHCII-CD43+Ly6C-Ly6G-Siglec-F- cells. They demonstrate similar ability as cDC to uptake and retain complex antigens like mannan via mannose receptors, but much lower ability to endocytose and retain soluble antigen. While L-DC differ from cDC by their inability to activate CD4+ T cells, they are capable of antigen cross-presentation for activation of CD8+ T cells, although less effectively so than the cDC subsets. In terms of gene expression, CD8- cDC and CD8+ cDC are quite distinct from L-DC. CD8+ cDC are distinguishable from the other two subsets by expression of CD24a, Clec9a, Xcr1 and Tlr11, while CD8- cDC are distinguished by expression of Ccnd1 and H-2Eb2. L-DC are distinct from the two cDC subsets through upregulated expression of Clec4a3, Emr4, Itgam, Csf1r and CD300ld. The L-DC gene profile is quite distinct from that of cDC, confirming a myeloid cell type with distinct antigen presenting properties.

Highlights

  • Dendritic cells (DC) play an important role in the immune system by acting as mediators between the innate and adaptive immune responses

  • While LDC differ from Conventional DC (cDC) by their inability to activate CD4+ Thy1.2 antibody/108 cells (T cells), they are capable of antigen cross-presentation for activation of CD8+ T cells, less effectively so than the cDC subsets

  • Based on previous identification studies, L-dendritic cells (DC) can be gated as a CD11bhiCD11cloLy6C-Ly6G-CD43+Siglec-F- subset (Fig 1) [20], and reflect myeloid lineage cells based on high expression of CD11b

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Summary

Introduction

Dendritic cells (DC) play an important role in the immune system by acting as mediators between the innate and adaptive immune responses. DC become activated by danger signals and recruit other leukocytes to sites of infection [2] Those that acquire infectious agents subsequently mount an antigen-specific T cell response against the pathogen [1, 2]. While several main DC lineages have been identified as professional antigen presenting cells (APC), increasingly novel APC are being identified in different tissues, each with specific functional capacity. Both humans and mice contain multiple subsets of DC, characterized by distinct capacity for antigen uptake, processing and presentation leading to T cell activation [1, 3]. The DC lineage is complex with distinct subtypes occupying different tissue locations, each with unique cell surface marker expression, migration potential, function in immunity and response

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