CD83 orchestrates immunity toward self and non-self in dendritic cells

Wild, Andreas B.; Krzyzak, Lena; Peckert, Katrin; Stich, Lena; Kuhnt, Christine; Butterhof, Alina; Seitz, Christine; Mattner, Jochen; Grüner, Niklas; Gänsbauer, Maximilian; Purtak, Martin; Soulat, Didier; Winkler, Thomas; Nitschke, Lars; Zinser, Elisabeth; Steinkasserer, Alexander

doi:10.1172/jci.insight.126246

Cited by 26 publications

(35 citation statements)

References 64 publications

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“…Among others, it was shown that these CD83 cKO mice cleared bacterial infections more rapidly than their wt counterparts and DCs from those mice produced more IL-12 (55). In line with these findings, we demonstrated aggravated autoimmune responses in mice with CD83-deficient DCs, which per se display an over-activated phenotype and drive inflammatory T cell responses, presumably by interfering with Treg function (56). This enhanced stimulatory potential of CD83-deficient DCs both in vitro and in vivo is intriguing considering the reduced surface expression of MHCII and CD86 on these cells, which normally is a prerequisite for efficient T cell activation.…”

Section: Cd83 and DC Activationsupporting

confidence: 88%

“…As mentioned above, the expression of CD83 on DCs is a critical determinant of the host immune response against bacteria. Mice with CD83-deficient DCs show improved resistance upon challenge with the extracellular enteropathogenic strain Citrobacter rodentium (55), and we further demonstrated enhanced clearance of intracellular bacteria like Salmonella or Listeria (56). In both settings, DCs from CD83 cKO mice react to bacterial challenge with increased expression of the cytokines IL-23 and IL-12.…”

Section: Bacteriamentioning

confidence: 58%

“…The authors suggested that upon binding to MD-2, sCD83 initiates an anti-inflammatory TLR-signaling cascade leading to long-term depletion of IRAK-1, which causes unresponsiveness to further TLR stimulation. Interestingly, Tregs that are devoid of CD83 display elevated levels of IRAK-1 (see chapter 4b) (38), and a similar phenotype is observed in CD83-deficient DCs (56). Subsequently, both cell types exhibit an aberrant activation profile and are prone to propagate autoreactive immune responses in the absence of CD83.…”

Section: Cd83 Binding Partners and Signaling Cascadesmentioning

confidence: 93%

“…This sorting procedure assures efficient antigen presentation in mDCs versus iDCs (61). Interestingly, murine conventional DCs (cDCs) with defective MHCII ubiquitination are less capable of inducing antigen-specific CD4 + T cell proliferation (58), whereas CD83 −/− DCs exhibited increased potential to stimulate antigen-dependent T cell responses (49,56).…”

Section: Cd83 and DC Activationmentioning

confidence: 99%

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The CD83 Molecule – An Important Immune Checkpoint

et al. 2020

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The CD83 molecule has been identified to be expressed on numerous activated immune cells, including B and T lymphocytes, monocytes, dendritic cells, microglia, and neutrophils. Both isoforms of CD83, the membrane-bound as well as its soluble form are topic of intensive research investigations. Several studies revealed that CD83 is not a typical co-stimulatory molecule, but rather plays a critical role in controlling and resolving immune responses. Moreover, CD83 is an essential factor during the differentiation of T and B lymphocytes, and the development and maintenance of tolerance. The identification of its interaction partners as well as signaling pathways have been an enigma for the last decades. Here, we report the latest data on the expression, structure, and the signaling partners of CD83. In addition, we review the regulatory functions of CD83, including its striking modulatory potential to maintain the balance between tolerance versus inflammation during homeostasis or pathologies. These immunomodulatory properties of CD83 emphasize its exceptional therapeutic potential, which has been documented in specific preclinical disease models.

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Section: Cd83 and DC Activationsupporting

confidence: 88%

Section: Bacteriamentioning

confidence: 58%

Section: Cd83 Binding Partners and Signaling Cascadesmentioning

confidence: 93%

Section: Cd83 and DC Activationmentioning

confidence: 99%

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The CD83 Molecule – An Important Immune Checkpoint

et al. 2020

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“…In this regard, several in vitro and in vivo studies revealed the immune-modulatory potential of the two known CD83 isoforms, i.e., the membrane-bound and soluble CD83 (sCD83). Particularly, the membranebound form of CD83 is pivotal for the thymic CD4 + T lymphocyte selection, via stabilizing MHC class II surface expression on thymic epithelial cells, and essential to suppress overshooting immune responses during the development or resolution of autoimmune disorders [42,[167][168][169]. Apart from this, sCD83 possesses an interesting therapeutic potential in order to prevent/resolve autoimmune disorders and to inhibit transplant rejection, which is mediated via the induction of regulatory mechanisms including indoleamine 2,3-dioxygenase (IDO)-induced regulatory T lymphocytes [170][171][172][173].…”

Section: Modulation Of Cd83 Expression In Mdcsmentioning

confidence: 99%

How Human Herpesviruses Subvert Dendritic Cell Biology and Function

Popella¹,

Steinkasserer²

2021

Innate Immunity in Health and Disease

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In the last decades, a multitude of distinct herpesvirus-mediated immune evasion mechanisms targeting dendritic cell (DC) biology were uncovered. Within this chapter, we summarize the current knowledge how herpesviruses, especially the α-herpesviruses HSV-1, HSV-2, varicella-zoster virus (VZV), and the β-herpesvirus HCMV, shape and exploit the function of myeloid DCs in order to hamper the induction of potent antiviral immune responses. In particular, the main topics covering herpesvirus-mediated immune evasion will involve: (i) the modulation of immature DC (iDC) phenotype, (ii) modulation of iDC apoptosis, (iii) the inhibition of DC maturation, (iv) degradation of the immune-modulatory molecule CD83 in mature DCs (mDCs), (v) interference with the negative regulator of β2 integrin activity, cytohesin-1 interaction partner (CYTIP), (vi) resulting in modulation of adhesion and migration of mDCs, (vii) autophagic degradation of lamins to support productive HSV-1 replication in iDCs, (viii) the release of uninfectious L-particles with immune-modulatory potential from HSV-1-infected mDCs, and (ix) the implications of DC subversion regarding T lymphocyte activation.

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Immunological tolerance and autoimmunity

Valdes

2022

Translational Autoimmunity

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CD83 orchestrates immunity toward self and non-self in dendritic cells

Cited by 26 publications

References 64 publications

The CD83 Molecule – An Important Immune Checkpoint

The CD83 Molecule – An Important Immune Checkpoint

How Human Herpesviruses Subvert Dendritic Cell Biology and Function

Immunological tolerance and autoimmunity

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