Exercising the immune system: Dendritic cells as mediators of the exercise-associated health benefits in patients with multiple sclerosis

Datum: 12 mei 2016

Locatie: UAntwerp - Campus Drie Eiken - Building Q - Promotiezaal - Universiteitsplein 1 - 2610 WILRIJK

Tijdstip: 18 uur

Organisatie / co-organisatie: Faculty of Medicine and Health Sciences

Promovendus: Nathalie Deckx

Promotor: Prof N. Cools, Prof P. Damme & Prof B. Op 't Eijnde

Korte beschrijving: PhD defence Nathalie Deckx - Faculty of Medicine and Health Sciences



Summary

Recently, many studies have demonstrated the role of the innate immune system, including dendritic cells (DC), in the immunopathogenesis of MS. Indeed, we and others recently demonstrated impaired Toll-like receptor (TLR) responsiveness of both conventional or myeloid DC (cDC) and plasmacytoid DC (pDC) in patients with MS. Since MS is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune response, different lifestyle changes, including physical exercise, are likely to influence the disease course of MS. MS patients participating in physical exercise programs displayed improvements in muscle strength, cardiovascular health, mental functioning and quality of life. To date, however, little is known about the potential effects of physical exercise on the underlying disease mechanisms.

We indicated an immediate increase of DC in the peripheral blood upon one bout of combined exercise in both MS patients and healthy subjects. Our results showed that mobilized DC are less responsive to TLR stimulation after one exercise bout, indicating that DC are less prone to drive inflammatory processes following acute physical activity. In addition, our results indicated an immediate increase of Treg in the peripheral blood upon one bout of combined exercise in both MS patients and healthy subjects.

In addition, we indicated decreased secretion of inflammatory mediators upon TLR stimulation in MS patients who participated in the 12-week combined exercise program. We hypothesized that this might contribute to a diminished stimulation of myelin-specific T helper (Th)1 and Th17 effector cells. Furthermore, increased cell counts of activated pDC were found after 12 weeks of exercise. Importantly, we demonstrated a positive correlation between the proportion of type 1 Treg (Tr1) and the number of circulating activated pDC. Since activated pDC are known to induce Tr1, we suggested that increasing numbers of activated pDC may drive the induction of Tr1 following long-term physical exercise in MS.

In conclusion, we demonstrated an important role of DC in the immune-suppressive effects of both acute and long-term physical activity in MS patients. Overall, we identify the DC as an important mediator of the exercise-induced immune changes. DC can play a role in altered T cell polarization following physical exercise, and thus lead to a shift in the balance between immunity and tolerance. Since this balance is disturbed in MS patients and DC play an important role in the pathogenesis of MS, we suggested here that physical activity is able to induce a favourable immunologic effect in MS patients.