Contributions
Abstract: P437
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Toll-like receptor 2 (TLR2) is an important innate immune receptor that can sense a broad spectrum of microbial as well as endogenous ligands due to its ability to heterodimerise with either TLR1 or TLR6. Multiple Sclerosis (MS) is an immune-mediated, inflammatory demyelinating disease of the central nervous system, in which pro-inflammatory Th17 cells appear to prevail over anti-inflammatory regulatory T cells (Tregs). Our lab has previously shown that TLR2 stimulation on human Tregs reduces their suppressive functions and can drive their differentiation towards a Th17-like phenotype and function. In addition, Tregs from relapsing-remitting MS (RRMS) patients are more susceptible to such TLR2-induced effects than those from healthy controls (HC). We are now expanding these studies to see whether these mechanisms are relevant in vivo.
In the HEK-293 transfection system and Dual luciferase reporter (DLR) assay, we identified some infectious stimuli including Helicobacter pylori, E. coli, S. aureus, S. epidermis, K. pneumoniae, P. aeruginosa, P. vulgaris as strong stimulants for TLR2, which could be associated with MS. We also tested the potential of urine and serum samples from MS patients and HC in the HEK-293 system to stimulate TLR2. Urine samples from MS patients in relapse contain higher TLR2-stimulating activity than HC; however, pilot paired samples from relapse and remission do not show significant differences. Besides, we are assessing the level of soluble TLR2 (sTLR2) as a potential biomarker of inflammation during MS relapses, measured both in serum and in urine by ELISA. In MS patients, sTLR2 levels are higher in urine during relapses than in remission, while in serum no significant differences were observed. We have collected paired relapse and remission samples from 25 RRMS patients to compare Treg and Th1/Th17 parameters by flow cytometry upon TLR2 stimulation in vitro in PBMCs and CD4+ T cells.
Disclosure: Conflict of interest statements:
Md Jakir Hossain: I am being supported by a McDonald Fellowship from Multiple Sclerosis International Federation (MSIF).
Elena Morandi: Nothing to disclose
Radu Tanasescu: Nothing to disclose
Clett Erridge: Noting to disclose
Tola A. Faraz: Nothing to disclose
Bruno Gran: I received research grant for this project from Italian Multiple Sclerosis Society (FISM Grant 2013/R/14)
Abstract: P437
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Immunology
Toll-like receptor 2 (TLR2) is an important innate immune receptor that can sense a broad spectrum of microbial as well as endogenous ligands due to its ability to heterodimerise with either TLR1 or TLR6. Multiple Sclerosis (MS) is an immune-mediated, inflammatory demyelinating disease of the central nervous system, in which pro-inflammatory Th17 cells appear to prevail over anti-inflammatory regulatory T cells (Tregs). Our lab has previously shown that TLR2 stimulation on human Tregs reduces their suppressive functions and can drive their differentiation towards a Th17-like phenotype and function. In addition, Tregs from relapsing-remitting MS (RRMS) patients are more susceptible to such TLR2-induced effects than those from healthy controls (HC). We are now expanding these studies to see whether these mechanisms are relevant in vivo.
In the HEK-293 transfection system and Dual luciferase reporter (DLR) assay, we identified some infectious stimuli including Helicobacter pylori, E. coli, S. aureus, S. epidermis, K. pneumoniae, P. aeruginosa, P. vulgaris as strong stimulants for TLR2, which could be associated with MS. We also tested the potential of urine and serum samples from MS patients and HC in the HEK-293 system to stimulate TLR2. Urine samples from MS patients in relapse contain higher TLR2-stimulating activity than HC; however, pilot paired samples from relapse and remission do not show significant differences. Besides, we are assessing the level of soluble TLR2 (sTLR2) as a potential biomarker of inflammation during MS relapses, measured both in serum and in urine by ELISA. In MS patients, sTLR2 levels are higher in urine during relapses than in remission, while in serum no significant differences were observed. We have collected paired relapse and remission samples from 25 RRMS patients to compare Treg and Th1/Th17 parameters by flow cytometry upon TLR2 stimulation in vitro in PBMCs and CD4+ T cells.
Disclosure: Conflict of interest statements:
Md Jakir Hossain: I am being supported by a McDonald Fellowship from Multiple Sclerosis International Federation (MSIF).
Elena Morandi: Nothing to disclose
Radu Tanasescu: Nothing to disclose
Clett Erridge: Noting to disclose
Tola A. Faraz: Nothing to disclose
Bruno Gran: I received research grant for this project from Italian Multiple Sclerosis Society (FISM Grant 2013/R/14)