Abstract
Dendritic cell–T cell (DC-T) contacts play an important role in T cell activation, clone generation, and development. Regulating the cytoskeletal protein rearrangement of DCs can modulate DC-T contact and affect T cell activation. However, inhibitory factors on cytoskeletal regulation in DCs remain poorly known. We showed that a soluble form of CD83 (sCD83) inhibited T cell activation by decreasing DC-T contact and synapse formation between DC and T cells. This negative effect of sCD83 on DCs was mediated by disruption of F-actin rearrangements, leading to alter expression and localization of major histocompatibility complex class II (MHC-II) and immunological synapse formation between DC and T cells. Furthermore, sCD83 was found to decrease GTP-binding activity of Rab1a, which further decreased colocalization and expression of LRRK2 and F-actin rearrangements in DCs, leading to the loss of MHC-II at DC-T synapses and reduced DC-T synapse formation. Further, sCD83-treated DCs alleviated symptoms of experimental autoimmune uveitis in mice and decreased the number of T cells in the eyes and lymph nodes of these animals. Our findings demonstrate a novel signaling pathway of sCD83 on regulating DC-T contact, which may be harnessed to develop new immunosuppressive therapeutics for autoimmune disease.
Highlights
Dendritic cells (DCs) play a crucial regulatory role in autoimmune disease and regulate the immune response by governing T cell activation or development
We demonstrate that soluble form of CD83 (sCD83) inhibits Immunological synapses (ISs) formation of DCs and T cells (DC-T) by disrupting the distribution of F-actin and major histocompatibility complex class II (MHC-II) at DC-T contacts, and we find that this inhibitory effect of sCD83 on DCs is via suppression of Rab1a, which controls the LRRK2 and F-actin colocalization
We found that sCD83 treatment decreased the increased percentage of CD11c+ MHC-II+ DCs and CD4+ T cells in the eyes and lymph nodes of infected mice (Figure 1A)
Summary
Dendritic cells (DCs) play a crucial regulatory role in autoimmune disease and regulate the immune response by governing T cell activation or development. Rab1a is found to control the actin cytoskeleton by regulating Roco kinase activity (Kicka et al, 2011), its major function is related to vesicle trafficking and autophagy (Ali et al, 2004; Webster et al, 2016). It indicates that Rab1a may participate to the DC-T IS formation. The regulatory mechanism of DC-T contact formation is still not very clear
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