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Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2017.201 Figure 2 The involvement of immune semaphorins in various aspects of immune responses Figure 2 | The involvement of immune semaphorins in various aspects of immune responses. During dendritic cell (DC) transmigration, SEMA3A binds to the plexin A1–neuropilin 1 (NRP1) receptor complex expressed on the rear sides of DCs, inducing their transmigration into the lymphatics. SEMA3E binds to plexin D1 expressed on thymocytes and contributes to thymocyte development by regulating thymocyte migration. SEMA4A regulates the differentiation of CD4+ T cells by amplifying T helper 1 (TH1) cell differentiation through the binding of T cell immunoglobulin and mucin domain-containing protein 2 (TIMD-2, also known as TIM-2) on TH1 cells. SEMA4A promotes the survival of regulatory T (Treg) cells by binding to NRP1 expressed by these cells. In the initial phase of T cell immune responses, SEMA4A expressed by DCs promotes the activation of T cells capable of recognizing alloantigens presented on DCs, through binding to TIMD-2 on activated T cells. SEMA4D expressed by T cells positively regulates humoral immune responses by activating B cells via CD72. SEMA4D expressed on T cells interacts with CD72 on DCs and promotes DC activation and maturation. SEMA7A is expressed on activated T cells and stimulates macrophages via integrins to produce pro-inflammatory cytokines. BCR, B cell receptor; TCR, T cell receptor. Nishide, M. & Kumanogoh, A. (2017) The role of semaphorins in immune responses and autoimmune rheumatic diseases Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2017.201