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Review
. 2023 Feb 1;24(3):2831.
doi: 10.3390/ijms24032831.

CD83 Regulates the Immune Responses in Inflammatory Disorders

Bushra Riaz  1 , S M Shamsul Islam  2 , Hye Myung Ryu  1 , Seonghyang Sohn  1   2
Affiliations
Review

CD83 Regulates the Immune Responses in Inflammatory Disorders

Bushra Riaz et al. Int J Mol Sci. .

Abstract

Activating the immune system plays an important role in maintaining physiological homeostasis and defending the body against harmful infections. However, abnormalities in the immune response can lead to various immunopathological responses and severe inflammation. The activation of dendritic cells (DCs) can influence immunological responses by promoting the differentiation of T cells into various functional subtypes crucial for the eradication of pathogens. CD83 is a molecule known to be expressed on mature DCs, activated B cells, and T cells. Two isotypes of CD83, a membrane-bound form and a soluble form, are subjects of extensive scientific research. It has been suggested that CD83 is not only a ubiquitous co-stimulatory molecule but also a crucial player in monitoring and resolving inflammatory reactions. Although CD83 has been involved in immunological responses, its functions in autoimmune diseases and effects on pathogen immune evasion remain unclear. Herein, we outline current immunological findings and the proposed function of CD83 in inflammatory disorders.

Keywords: CD83; dendritic cell; herpes simplex virus; inflammatory disease.

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Conflict of interest statement

Authors declare no competing interests.

Figures

Figure 1
Figure 1
CD83 knockout (KO) mice model displayed abnormal tolerance. (a) CD83 KO TEC showed a strongly decreased number of CD4+ T cells and deletion of MARCH 8 in CD83KO TEC restored CD4+ T cells. (b) In CD83 cKO mice, CD83 is only ablated in Treg cells, and expression of Treg-specific maturation biomarkers (CD25, CD103, CD62L, or KLRG1) and transcriptional factors (Blimp-1, Foxp3, GATA, and Smarcd 3) are reduced. Signaling pathway (IRAK1), inflammatory cytokines (TNF-α, IL-1β, IFN-γ, IL-22), and other biomarkers (CD44, CD69, Tlr13) were present at high levels. (c) CD83 KO B cells have reduced IL-10, MHC II, CD86 expression levels, and increased Ig levels. (d) CD83 KO DCs expressed higher levels of costimulatory molecules (OX40L, CD25) and transcription factors (IRAK1, Nfatc2) and significantly more cytokines (IL-2, IL-17A, IL-6, TNF-α) were secreted. Overall, CD83 expression is essential for ongoing immunological responses. TECs, thymic-epithelial cells; MARCH 8, membrane-associated RING-CH-type protein; KLRG1, killer-cell lectin-like-receptor subfamily-G-member-1; IRAK1, Interleukin 1 Receptor Associated Kinase 1; Tlr, Toll-like receptor; TNF-α, tumor-necrosis factor-α; IL-1β, interleukin-1-beta; IFN-γ, interferon gamma MHC, major-histocompatibility complex; Ig, immunoglobulin; IL, interleukin.
Figure 2
Figure 2
Correlation between CD83 and HSV. (a) HSV-1 proteins vhs and ICP0 degraded the CD83 on iDC and matDC, respectively. Uninfected-bystander matDCs showed a significant CD83 reduction because L-particles are released from infected matDCs. Uninfected bystander matDCs and infected matDCs prevent T cell activation. (b) HSV-2 infection on moDCs reduced CD83 levels and enhanced cytokine and protein levels (TNF-α, IL-6, CCL3), further attenuating the T cell responses. When glycoprotein-D deleted HSV-2 virus is exposed to DCs, T cell stimulation is enhanced. HSV, Herpes simplex virus; vhs, host-shutoff protein; ICPO, infected-cell protein-0; moDCs, monocyte-derived-DCs; TNF-α, tumor-necrosis factor-α; IL-6, interleukin-6; CCL3, Chemokine ligand 3.
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Grants and funding

This was supported by a grant (2020R1A2C2012721) through the NRF funded by the Ministry of Science and ICT (MIST), Republic of Korea.

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