Antigen presentation by dendritic cells and their instruction of CD4+ T helper cell responses

Hilligan, Kerry L.; Ronchese, Franca

doi:10.1038/s41423-020-0465-0

Cited by 250 publications

(177 citation statements)

References 264 publications

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“…Human DCs commonly express the major histocompatibility complex (MHC) molecule, human leukocyte antigen (HLA)-DR, cluster of differentiation (CD) 209 and integrin CD11c, which can also be found on subsets of macrophages, activated T cells, B cells and natural killer (NK) cells [ 3 ]. There is a great heterogeneity of DC populations, depending on the developmental lineage, differentiation stage and the influence of surrounding tissue [ 24 ]. The main subsets of DC are generally distinguished by the combination of the four markers BDCA-1 (CD1c), BDCA-2 (CD303), BDCA-3 (CD141) and BDCA-4 (CD304).…”

Section: Crosstalk Of Dcs and T Cellsmentioning

confidence: 99%

Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer

Lurje

Hammerich

Tacke

2020

IJMS

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Liver fibrosis is a chronic, highly prevalent disease that may progress to cirrhosis and substantially increases the risk for development of hepatocellular carcinoma (HCC). Fibrotic livers are characterized by an inflammatory microenvironment that is composed of various immunologically active cells, including liver-resident populations (e.g., Kupffer cells, hepatic stellate cells and sinusoidal endothelium) and infiltrating leukocytes (e.g., monocytes, monocyte-derived macrophages, neutrophils and lymphocytes). While inflammatory injury drives both fibrogenesis and carcinogenesis, the tolerogenic microenvironment of the liver conveys immunosuppressive effects that encourage tumor growth. An insufficient crosstalk between dendritic cells (DCs), the professional antigen presenting cells, and T cells, the efficient anti-tumor effector cells, is one of the main mechanisms of HCC tumor tolerance. The meticulous analysis of patient samples and mouse models of fibrosis-HCC provided in-depth insights into molecular mechanisms of immune interactions in liver cancer. The therapeutic modulation of this multifaceted immunological response, e.g., by inhibiting immune checkpoint molecules, in situ vaccination, oncolytic viruses or combinations thereof, is a rapidly evolving field that holds the potential to improve the outcome of patients with HCC. This review aims to highlight the current understanding of DC–T cell interactions in fibrogenesis and hepatocarcinogenesis and to illustrate the potentials and pitfalls of therapeutic clinical translation.

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Section: Crosstalk Of Dcs and T Cellsmentioning

confidence: 99%

Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer

Lurje

Hammerich

Tacke

2020

IJMS

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“…The differentiation of CD4+ T cells into distinct functional populations is a key event in adaptive immunity: IFNγ+ T helper (Th)1 cells clear intracellular pathogens and some bacterial infections, while IL-4+ Th2 and IL-17+ Th17 cells respond to helminth and fungal infections, respectively 1 . The context of antigen recognition is a major factor in determining CD4+ T cell differentiation 2 , 3 . Through the expression of pattern recognition and cytokine receptors, antigen-presenting cells (APCs) perceive pathogens while sensing the response of bystander cells to the same stimuli 4 , thereby conveying the sum of these signals to initiate the appropriate CD4+ T cell differentiation program.…”

Section: Introductionmentioning

confidence: 99%

Dermal IRF4+ dendritic cells and monocytes license CD4+ T helper cells to distinct cytokine profiles

et al. 2020

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Antigen (Ag)-presenting cells (APC) instruct CD4+ helper T (Th) cell responses, but it is unclear whether different APC subsets contribute uniquely in determining Th differentiation in pathogen-specific settings. Here, we use skin-relevant, fluorescently-labeled bacterial, helminth or fungal pathogens to track and characterize the APC populations that drive Th responses in vivo. All pathogens are taken up by a population of IRF4+ dermal migratory dendritic cells (migDC2) that similarly upregulate surface co-stimulatory molecules but express pathogen-specific cytokine and chemokine transcripts. Depletion of migDC2 reduces the amount of Ag in lymph node and the development of IFNγ, IL-4 and IL-17A responses without gain of other cytokine responses. Ag+ monocytes are an essential source of IL-12 for both innate and adaptive IFNγ production, and inhibit follicular Th cell development. Our results thus suggest that Th cell differentiation does not require specialized APC subsets, but is driven by inducible and pathogen-specific transcriptional programs in Ag+ migDC2 and monocytes.

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“…More likely, however, niches exist within organs in which cytokines are restricted due to their precise expression by distinct cellular sources. 109,[135][136][137] The DC sources of these cytokines that act to facilitate Tfh and Th1 fate commitment have been recently reviewed elsewhere. 127,136 It is, however, important to note that the cellular sources of cytokines, such as IL-12 and IL-6, are not restricted to a single DC subset.…”

Section: Discussionmentioning

confidence: 99%

Transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment

Sheikh

Groom

2020

Cell Mol Immunol

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During viral infection, immune cells coordinate the induction of inflammatory responses that clear infection and humoral responses that promote protection. CD4+ T-cell differentiation sits at the center of this axis. Differentiation toward T-helper 1 (Th1) cells mediates inflammation and pathogen clearance, while T follicular helper (Tfh) cells facilitate germinal center (GC) reactions for the generation of high-affinity antibodies and immune memory. While Th1 and Tfh differentiation occurs in parallel, these CD4+ T-cell identities are mutually exclusive, and progression toward these ends is determined via the upregulation of T-bet and Bcl6, respectively. These lineage-defining transcription factors act in concert with multiple networks of transcriptional regulators that tip the T-bet and Bcl6 axis in CD4+ T-cell progenitors to either a Th1 or Tfh fate. It is now clear that these transcriptional networks are guided by cytokine cues that are not only varied between distinct viral infections but also dynamically altered throughout the duration of infection. Thus, multiple intrinsic and extrinsic factors combine to specify the fate, plasticity, and function of Th1 and Tfh cells during infection. Here, we review the current information on the mode of action of the lineage-defining transcription factors Bcl6 and T-bet and how they act individually and in complex to govern CD4+ T-cell ontogeny. Furthermore, we outline the multifaceted transcriptional regulatory networks that act upstream and downstream of Bcl6 and T-bet to tip the differentiation equilibrium toward either a Tfh or Th1 fate and how these are impacted by dynamic inflammatory cues.

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Antigen presentation by dendritic cells and their instruction of CD4+ T helper cell responses

Cited by 250 publications

References 264 publications

Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer

Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer

Dermal IRF4+ dendritic cells and monocytes license CD4+ T helper cells to distinct cytokine profiles

Transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment

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