CONICET | Buscador de Institutos y Recursos Humanos

INVESTIGADORES

ERRASTI Andrea Emilse

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Título:

ROLE OF PROTEIN S AND TYRO3 RECEPTOR TYROSINE KINASE IN THE PATHOGENESIS OF MULTIPLE SCLEROSIS AND THE TYPE-2 PROTECTIVE ENVIRONMENT

Autor/es:

JUAN MANUEL ORTIZ WILCZYÑSKI ; CINTHIA MARIEL OLEXEN; ANDREA EMILSE ERRASTI; MIRTA SCHATTNER; CARLA V. ROTHLIN; JORGE CORREALE; ANTONIO E. CARRERA SILVA

Lugar:

Mar del Plata

Reunión:

Congreso; Reunión Conjunta SAIC-SAI-SAFE 2016; 2016

Institución organizadora:

SAIC-SAI-SAFE

Resumen:

Multiple sclerosis (MS)is a chronic inflammatory and autoimmune disorder causing central nervoussystem demyelination and axonal injury by infiltration of autoreactive Th1/Th17cells. The inflammatory environment is the main driver of damage and loss ofneurologic function. Interestingly, helminth-infected MS patients showed lowernumber of relapses, lesion activity and minimal changes in disability scorescompared with uninfected individuals with MS. Parasite-driven protection wasassociated with a reduction of pro-inflammatory cytokines via SOCS3, inductionof Tregs and IL-10. TYRO3, AXL and MERTK (TAM) tyrosine kinase receptors andits ligand Protein S (PROS1) are critical regulators of the immune response andwe have recently demonstrated that Th2 environment enhances PROS1 and TYRO3expression. We hypothesize that the engagement of PROS1-TYRO3 axis will beenhanced during helminth infection negatively regulating an associatedinflammatory response Th1/Th17. We evaluated TAM receptors and PROS1 expressionin peripheral blood monocytes, dendritic and T cells compartment of patientswith diagnosed MS (N=18), helminth-infected patients (HP, N=8) and healthycontrols (HC, N=13-20). We found a significant increased level of PROS1 andMERTK in blood CD4 T cells of MS patients compared to HC. However, afterin-vitro TCR activation, CD4 T cells from MS induced lower levels of PROS1 (100.3± 5.6)vs HC (120.7± 2.6) or HP (137.8 ± 6.0) measured as meanfluorescence intensity. Furthermore, PROS1 levels in CD4+/IFNg+and CD4+/IL13+ was higher in HP > HC > MS. Interesting,CD1c dendritic cells showed higher TYRO3 expression in HP (10.4 ± 0.9) vs HC (6.5 ± 0.3) and MS (4.9 ± 0.3) measured as foldincrease referred to isotype. Our results suggest that the enhanced PROS1/TYRO3axis in HP could be favoring a more efficient engagement of this anti-inflammatorypathway and could contribute to explain the parasite-driven protection observedin helminth-infected MS.

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