Figure 3.

Innate and adaptive crosstalk. Activated SGECs secrete BAFF that promotes the activation and maturation of B cells into long-lasting memory B cells and plasma B cells producing auto-antibodies. SGECs also produce chemokines IL-1, IL-6, IL18, and TNFα that attract immune cells and contribute to the formation of germinal centers. Activated SGECs have the ability to act as non-professional antigen-presenting cells by expressing MHC-I (HLA-ABC) and MHC-II (HLA-DR) adhesion molecules such as ICAM1, allowing them to activate T cells. TLR activation also contributes to SGEC apoptosis, releasing autoantigens that drive autoimmunity in pSS. Activated macrophages can act as antigenic peptide presenting cells through their MHC-II and interact with antigen-specific CD4+ T cells. pDCs lead to the production of type I IFN that acts through autocrine and paracrine circuits feeding a continuous reinforcing inflammatory loop. It also induces BAFF production, contributing to the activation of B cells into plasma cells. DCs also play an essential part in the structure of ectopic germinal centers and retain on their surface immune-complexes, formed by antigen-antibody-complement.