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

The CD83 Molecule – An Important Immune Checkpoint

“…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.…”

“…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.…”

“…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.…”

“…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).…”

How Human Herpesviruses Subvert Dendritic Cell Biology and Function

“…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].…”