1 | The effect of polarisation on the infiltration of monocytes into the CNS

In multiple sclerosis (MS) myeloid cells invade the inflamed CNS and the brain barriers function as checkpoints to control their invasion. This project will investigate if CNS interfaces distinguish between differentially polarized myeloid cells, and the distinct role of invading and resident phagocytes during neuroinflammation at brain barriers and in the parenchyma. We will use innovative transgenic approaches to track polarised myeloid cells and visualise their infiltration across brain barriers by 2-photon and light-sheet microscopy in experimental autoimmune encephalomyelitis (EAE), an MS model.

Publications

• Haghayegh Jahromi N; Tardent H, Enzmann G, Deutsch U, Kawakami N, Bittner S, Vestweber D, Zipp F, Stein JV, Engelhardt B. A novel cervical spinal cord window preparation allows for two-photon imaging of T-cell interactions with the cervical spinal cord microvasculature during experimental autoimmune encephalomyelitis. Front Immunol 2017;8:406.
• Lyck R, Lécuyer MA, Abadier M, Wyss CB, Matti C, Rosito M, Enzmann G, Zeis T, Michel L, Garcia A, Sallusto F, Gosselet F, Deutsch U, Weiner JA, Schaeren-Wiemers N, Prat A, Engelhardt B.. ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood-brain barrier. J Cereb Blood Flow Metab 2016;37:2894-2909.
• Tietz S, Périnat T, Greene G, Enzmann G, Deutsch U, Adams R, Imhof B, Aurrand-Lions M, Engelhardt B. Lack of Junctional Adhesion Molecule (JAM)-B ameliorates experimental autoimmune encephalomyelitis. Brain Behavior Immunity 2018; pii: S0889-1591(18)30230-7. doi: 10.1016/j.bbi.2018.06.014.
• Lazarevic I and B Engelhardt. Modeling immune functions of the mouse blood-cerebrospinal fluid barrier in vitro: primary rather than immortalized mouse choroid plexus epithelial cells are suitable to study immune cell migration across this brain barrier. Fluids Barriers CNS 2016;13:2.
• Goldmann T, Wieghofer P, Jordao MJ, Prutek F, Hagemeyer N, Frenzel K, Amann L, Staszewski O, Kierdorf K, Krüger M, Locatelli G, Hochgerner H, Zeiser R, Epelman S, Geismann F, Priller J, Rossi FM, Bechmann I, Kerschensteiner M, Linnarsson S, Jung S, Prinz M. Origin, fate and dynamics of macrophages at central nervous system interfaces. Nat Immunol 2016;17:797-805.
• Locatelli G, Theodorou D, Jordao MJ, Staszewski O, Dagkalis A, Bessis A, Prinz M, and Kerschensteiner M. Mononuclear phagocytes locally specify and adapt their phenotypes in the inflamed central nervous system. Nat Neuro 2018:1-3.

Potential secondments

UKLFR (Marco Prinz), month 10-12; MIM (Paul Vulto), month 24-26.