Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology

Asselin‐Paturel, Carine; Boonstra, André; Dalod, Marc; Durand, Isabelle; Yessaad, Nadia; Dezutter‐Dambuyant, Colette; Vicari, Alain; O’Garra, Anne; Biron, Christine A.; Brière, Francine; Trinchieri, Giorgio

doi:10.1038/ni736

Cited by 904 publications

(824 citation statements)

References 28 publications

Supporting

Mentioning

785

Contrasting

Unclassified

Order By: Relevance

“…Also, according to previously published work, murine plasmacytoid dendritic cells (PDCs) could also be found among the CD11c-low/low-autofluorescent population (30). Our preliminary observations indicate that the naïve mouse lung contains a small population of cells that fit the immunophenotype of murine PDCs, i.e., CD11c-low, CD11b-, B220ϩ, and Gr-1ϩ (Ͻ0.1% of total lung cells).…”

Section: Figsupporting

confidence: 78%

Accurate and simple discrimination of mouse pulmonary dendritic cell and macrophage populations by flow cytometry: Methodology and new insights

2004

View full text Add to dashboard Cite

BackgroundThe need to accurately discriminate dendritic cells (DCs) and macrophages (Mphs) in mouse lungs is critical given important biological differences. However, a validated flow cytometry–based method is still lacking, resulting in much confusion between both cell types.MethodsSingle‐cell suspensions freshly obtained from collagenase‐digested lung tissue were stained with a CD11c‐specific monoclonal antibody, detected using a PE‐Cy5 or APC‐conjugated secondary reagent. Cellular immunophenotype was simultaneously explored using a panel of PE‐conjugated markers. The FL1 or FITC‐detection channel was reserved for the assessment of autofluorescence.ResultsCD11c‐bright cells were heterogeneous and displayed a bimodal distribution with regard to autofluorescence (AF). CD11c+/low‐AF cells were lineage‐negative and showed features compatible with myeloid DCs. This was confirmed by morphology, potent T‐cell stimulatory function in a mixed‐leukocyte reaction, surface expression of MHCII and costimulatory molecules, and further immunophenotypical criteria, including the expression of Mac‐1 and absence of CD8α. In contrast, CD11c+/high‐AF cells displayed the features of pulmonary Mphs, including typical Mph morphology, very weak induction of T‐cell proliferation, low to absent expression of MHCII and costimulatory molecules, and very low levels of Mac‐1 as well as F4/80. We also show that only CD11c+/high‐AF cells strongly expressed the macrophage marker MOMA‐2, while interestingly Mac‐3 was expressed at high levels by CD11c+/high‐AF and low‐AF alike.ConclusionsThis study shows that the combination of CD11c‐expression and autofluorescence is necessary and sufficient to accurately separate DCs from macrophage subpopulations in mouse lungs. © 2004 Wiley‐Liss, Inc.

show abstract

Section: Figsupporting

confidence: 78%

Accurate and simple discrimination of mouse pulmonary dendritic cell and macrophage populations by flow cytometry: Methodology and new insights

2004

View full text Add to dashboard Cite

show abstract

“…These three subsets are referred in the literature as spleen conventional DC. A fourth DC subset, the plasmacytoid DC express low levels of CD11c and the B220 markers and are also resident in the spleen [4]. The plasmacytoid DC subset is specialized in the secretion of type I interferons in response to viral and bacterial pathogens.…”

Section: Dendritic Cellsmentioning

confidence: 99%

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

Trez

Ware

2008

Cytokine & Growth Factor Reviews

View full text Add to dashboard Cite

Dendritic cells (DC) constitute the most potent antigen presenting cells of the immune system, playing a key role bridging innate and adaptive immune responses. Specialized DC subsets differ depending on their origin, tissue location and the influence of trophic factors, the latter remain to be fully understood. Stromal cell and myeloid-associated Lymphotoxin-β receptor (LTβR) signaling is required for the local proliferation of lymphoid tissue DC. This review focuses the LTβR signaling cascade as a crucial positive trophic signal in the homeostasis of DC subsets. The noncanonical coreceptor pathway comprised of the Immunoglobulin (Ig) superfamily member, B and T lymphocyte attenuator (BTLA) and TNFR superfamily member, Herpesvirus entry mediator (HVEM) counter regulates the trophic signaling by LTβR. Together both pathways form an integrated signaling circuit achieving homeostasis of DC subsets.Keywords dendritic cells; homeostasis; TNF superfamily; cosignaling; lymphotoxin; herpesvirus entry mediator Dendritic CellsDendritic cells (DC) originate from hematopoietic precursors and can be divided in several subsets depending on their anatomical location, surface phenotype and function. For example, two broad classes of DC are the peripheral migratory DC and the lymphoid tissue-resident DC [1]. The migratory DC, i.e. the dermal DC and Langerhans cells, can be considered as sentinels of the immune system as they form a sensing barrier in peripheral tissues at the interface with environment. The lymphoid tissue-resident DC include the splenic and thymic DC.Dendritic cells are specialized in the capture, transport, processing and presentation of antigens. In the presence of a microbial stimulus, these steps are associated with further DC differentiation (maturation) characterized by upregulation of costimulatory and major histocompatibility complex (MHC) molecules. As DC become activated they migrate to or Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Both spleen and lymph node lymphoid tissue-resident DC possess a half-life of about three days. Despite their rapid turnover, little is known about the factors controlling immediate precursors and homeostasis in vivo. In earlier studies, CD8α expression was used to distinguish between "lymphoid" and "myeloid" DC. However, more recent experiments showed that different DC subsets could differentiate from both lymphoid and myeloid precursors [6,7]. CD8α marker remains very useful to discriminate between subsets, but no longer defines a subset origin. Recently, the group of Shortman provided in vivo and in vitro evidence fo...

show abstract

“…4A-C). Two additional pDC markers (Ly6C [24] and mPDCA-1), expressed on both Ly49Q + and Ly49Q -pDC from the bone marrow (Fig. 4B), were used to verify the identity of the pDC; contamination by NK cell precursors, which also express CD11c and B220 [25,26], was ruled out by staining for CD122, another marker of NK cell precursors [27] (Fig.…”

Section: Bone Marrow Cells Cultured With Flt3l Secrete Type I Ifnmentioning

confidence: 99%

Type I interferon regulates pDC maturation and Ly49Q expression

Toma-Hirano

Namiki²,

Miyatake

et al. 2007

Eur J Immunol

View full text Add to dashboard Cite

Ly49Q is expressed on peripheral mouse plasmacytoid dendritic cells (pDC). Immature Ly49Q-negative pDC precursors acquire Ly49Q in the bone marrow and then migrate into the periphery. While searching for molecules that regulate pDC maturation, we found that type I interferon (IFN) inhibited Ly49Q acquisition in vitro. Infections that induce type I IFN production by cells other than pDC (a condition mimicked by poly(I:C) injection in vivo) increase the prevalence of Ly49Q -pDC in the bone marrow and peripheral lymphoid organs in wild-type but not IFN-a/b receptor knockout BALB/c mice. Moreover, in vivo exposure to type I IFN causes some Ly49Q -, but not Ly49Q + , pDC to convert to conventional DC, defined as B220 -CD11c + CD11b + cells. These data suggest that type I IFN regulates pDC development and affects their distribution in the body.

show abstract

Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology

Cited by 904 publications

References 28 publications

Accurate and simple discrimination of mouse pulmonary dendritic cell and macrophage populations by flow cytometry: Methodology and new insights

Accurate and simple discrimination of mouse pulmonary dendritic cell and macrophage populations by flow cytometry: Methodology and new insights

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

Type I interferon regulates pDC maturation and Ly49Q expression

Contact Info

Product

Resources

About