Plasmacytoid dendritic cells and autoimmune inflammation

Abstract Plasmacytoid dendritic cells (pDC) are a sub-population of dendritic cells (DC) that produce large amounts of type I interferon (IFN) in response to nucleic acids that bind and activate toll-like-receptor (TLR)9 and TLR7. Type I IFN can regulate the function of B, T, DC, and natural killer (NK) cells and can also alter the residence time of leukocytes within lymph nodes. Activated pDC can also function as antigen presenting cells (APC) and have the potential to prime and differentiate T cells into regulatory or inflammatory effector cells, depending on the context. In this review we discuss pDC ontogeny, function, trafficking, and activation. We will also examine how pDC can potentially be involved in regulating immune responses in the periphery as well as within the central nervous system (CNS) during multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE).

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Cell-intrinsic role for IFN-α–STAT1 signals in regulating murine Peyer patch plasmacytoid dendritic cells and conditioning an inflammatory response

Blood ◽

10.1182/blood-2011-04-349761 ◽

2011 ◽

Vol 118 (14) ◽

pp. 3879-3889 ◽

Cited By ~ 32

Author(s):

Haiyan S. Li ◽

Alexander Gelbard ◽

Gustavo J. Martinez ◽

Eiji Esashi ◽

Huiyuan Zhang ◽

...

Keyword(s):

Dendritic Cells ◽

Plasmacytoid Dendritic Cells ◽

Type I Interferons ◽

Type I ◽

Toll Like Receptor ◽

Ccr9 Expression ◽

A Cell ◽

And Function ◽

Antigen Presenting

Abstract Plasmacytoid dendritic cells (pDCs) reside in bone marrrow and lymphoid organs in homeostatic conditions and typically secrete abundant quantities of type I interferons (IFNs) on Toll-like receptor triggering. Recently, a pDC population was identified within Peyer patches (PPs) of the gut that is distinguished by its lack of IFN production; however, the relationship of PP pDCs to pDCs in other organs has been unclear. We report that PP pDCs are derived from common DC progenitors and accumulate in response to Fms-like tyrosine kinase 3 ligand, yet appear divergent in transcription factor profile and surface marker phenotype, including reduced E2-2 and CCR9 expression. Type I IFN signaling via STAT1 has a cell-autonomous role in accrual of PP pDCs in vivo. Moreover, IFN-α enhances pDC generation from DC progenitors by a STAT1-dependent mechanism. pDCs that have been developed in the presence of IFN-α resemble PP pDCs, produce inflammatory cytokines, stimulate Th17 cell generation, and fail to secrete IFN-α on Toll-like receptor engagement. These results indicate that IFN-α influences the development and function of pDCs by inducing emergence of an inflammatory (Th17-inducing) antigen-presenting subset, and simultaneously regulating accumulation of pDCs in the intestinal microenvironment.

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Faculty Opinions recommendation of Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1123432.582895 ◽

2008 ◽

Author(s):

Adolfo Garcia-Sastre

Keyword(s):

Dendritic Cells ◽

Type I Interferon ◽

Plasmacytoid Dendritic Cells ◽

Type I ◽

Toll Like Receptor

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Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis

Acta Neuropathologica ◽

10.1007/s00401-015-1418-z ◽

2015 ◽

Vol 130 (1) ◽

pp. 107-118 ◽

Cited By ~ 42

Author(s):

Reza Khorooshi ◽

Marlene Thorsen Mørch ◽

Thomas Hellesøe Holm ◽

Carsten Tue Berg ◽

Ruthe Truong Dieu ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Experimental Autoimmune Encephalomyelitis ◽

Type I Interferon ◽

Protective Role ◽

Type I ◽

Autoimmune Encephalomyelitis ◽

The Central Nervous System ◽

Experimental Autoimmune

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Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction

Journal of Experimental Medicine ◽

10.1084/jem.20090547 ◽

2009 ◽

Vol 206 (7) ◽

pp. 1603-1614 ◽

Cited By ~ 201

Author(s):

Wei Cao ◽

Laura Bover ◽

Minkwon Cho ◽

Xiaoxia Wen ◽

Shino Hanabuchi ◽

...

Keyword(s):

Dendritic Cells ◽

Proinflammatory Cytokines ◽

Stromal Cell ◽

Bone Marrow Stromal Cell ◽

Type I Interferon ◽

Plasmacytoid Dendritic Cells ◽

Orphan Receptor ◽

Receptor Interaction ◽

Type I ◽

Toll Like Receptor

Plasmacytoid dendritic cells (pDCs) produce copious type I interferon (IFN) upon sensing nucleic acids through Toll-like receptor (TLR) 7 and TLR9. Uncontrolled pDC activation and IFN production are implicated in lymphopenia and autoimmune diseases; therefore, a mechanism controlling pDC IFN production is essential. Human pDCs specifically express an orphan receptor, immunoglobulin-like transcript 7 (ILT7). Here, we discovered an ILT7 ligand expressed by human cell lines and identified it as bone marrow stromal cell antigen 2 (BST2; CD317). BST2 directly binds to purified ILT7 protein, initiates signaling via the ILT7–FcεRIγ complex, and strongly inhibits production of IFN and proinflammatory cytokines by pDCs. Readily induced by IFN and other proinflammatory cytokines, BST2 may modulate the human pDC’s IFN responses through ILT7 in a negative feedback fashion.

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