PURPOSE: The nature of triggers activating auto-aggressive lymphocytes in Multiple Sclerosis is poorly understood, but both environment and genetic factors are relevant. The role of infectious agents in the regulation of T cell trafficking is currently unknown. We showed that the amount of M tuberculosis in the adjuvant modulates rapid relocation of antigen-specific T cells, and that this mobilization is influenced by a non-synonymous polymorphism of TLR2 (Ile82Met) (1). Here we explore the role of TLR2 polymorphism in the regulation of alternative splicing of CD44. METHODS: We used SJL, B6 and B6 knock-out for Toll like receptor 2 (TLR2) or for MYD88. Cells were stimulated with different TLR ligands. We analyzed the CD44 isoforms expression with a quantitative PCRs (TaQman technology). RESULTS: We examined the expression of activation markers and adhesion molecules involved in T cell trafficking and we found that the early relocation is associated with intermediate expression of CD44. TLR selectively regulates the expression of CD44e and CD44f isoforms on T cells. Peptidoglycan modulates these isoforms exclusively through TLR2 and this mechanism is MYD88 dependent. CD44f expression is preferentially regulated by TLR2/TLR1 dimer. TLR9 upregulates preferentially CD44e. DISCUSSION: Our results show that pathogens engaging TLRs in activated T cells (through a polymorphic site) regulate effector T cells trafficking in vivo and in parallel modulate expression of CD44e and CD44f. CONCLUSION: The pathways TLR2-CD44 isoforms and their ligands may play a critical role in relating environment to acute presentation of autoimmune diseases, and may ultimately modulate severity and course of the disease. Interference with this pathway (polymorphic variants of these molecules or treatment with specific agonists) may represent an interesting target for diagnostic and therapy in the management of human disease. BIBLIOGRAPHY: 1 Nicolò, et al. PLoS One. 2013;8(2)
The pathway Toll like receptor 2 - CD44: a pathogenetic mechanism and therapeutic target for inflammation in autoimmune disease
DI SANTE G;
2014
Abstract
PURPOSE: The nature of triggers activating auto-aggressive lymphocytes in Multiple Sclerosis is poorly understood, but both environment and genetic factors are relevant. The role of infectious agents in the regulation of T cell trafficking is currently unknown. We showed that the amount of M tuberculosis in the adjuvant modulates rapid relocation of antigen-specific T cells, and that this mobilization is influenced by a non-synonymous polymorphism of TLR2 (Ile82Met) (1). Here we explore the role of TLR2 polymorphism in the regulation of alternative splicing of CD44. METHODS: We used SJL, B6 and B6 knock-out for Toll like receptor 2 (TLR2) or for MYD88. Cells were stimulated with different TLR ligands. We analyzed the CD44 isoforms expression with a quantitative PCRs (TaQman technology). RESULTS: We examined the expression of activation markers and adhesion molecules involved in T cell trafficking and we found that the early relocation is associated with intermediate expression of CD44. TLR selectively regulates the expression of CD44e and CD44f isoforms on T cells. Peptidoglycan modulates these isoforms exclusively through TLR2 and this mechanism is MYD88 dependent. CD44f expression is preferentially regulated by TLR2/TLR1 dimer. TLR9 upregulates preferentially CD44e. DISCUSSION: Our results show that pathogens engaging TLRs in activated T cells (through a polymorphic site) regulate effector T cells trafficking in vivo and in parallel modulate expression of CD44e and CD44f. CONCLUSION: The pathways TLR2-CD44 isoforms and their ligands may play a critical role in relating environment to acute presentation of autoimmune diseases, and may ultimately modulate severity and course of the disease. Interference with this pathway (polymorphic variants of these molecules or treatment with specific agonists) may represent an interesting target for diagnostic and therapy in the management of human disease. BIBLIOGRAPHY: 1 Nicolò, et al. PLoS One. 2013;8(2)I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
