Multiple Sclerosis is a chronic, inflammatory demyelinating disease of the human central nervous system, affecting mostly young adults in the prime of their lives. Its clinical manifestation is characterized mainly by motor and sensory deficits, and most commonly has a relapsing-remitting course. Although there is a debate on the immunological versus neurodegenerative origin of MS, it is well-established that the entry of leukocytes into the CNS is an important event in the pathophysiology of MS, in addition to glial cell activation. In active white matter MS lesions, a disturbance of the bloodbrain barrier function permits this influx of immunomodulatory cells, contributing to inflammation, demyelination and axonal damage evoking neurological deficits. In grey matter lesions, the influx of immunomodulatory cells is rather limited, whereas activated microglial cells are present like in white matter lesions but to a lesser extent. ECM proteins are generally important because they play a role in the recruitment of inflammatory cells by interacting with integrins expressed on activated leukocytes. This interaction occurs via the recognition site amino acid motif Arg-Gly-Asp that can be found within FN and many other matrix proteins. In this manner, TG2 can contribute to cell-matrix interactions such as cell adhesion and possibly other b-integrin-dependent functions including cell spreading and migration of e.g. monocytes that likely are of importance during MS lesion formation. In the present study, we therefore question whether TG2 is present in various lesion types in experimental autoimmune encephalomyelitis in the common marmoset. This experimental animal model mimics relevant clinical symptoms and relevant inflammatory, glial, and demyelinating white and grey matter pathology associated with relapsing-remitting MS which is uncommon in rodent models for MS. To this end, we studied the presence of immunoreactive TG2 in white and grey matter lesions of marmosets suffering from EAE, identified the cell types expressing TG2, and related those to FN and b1-integrin expression. The present study shows appearance of TG2 immunoreactivity in monocyte and microglial-like cells in early active white matter, and active grey matter marmoset EAE lesions. When white matter lesions progress to late active and inactive stages, TG2 immunoreactivity is still present, but in the inactive lesions it is significantly less pronounced. In addition, in white matter lesions, TG2 positive monocytes Masitinib co-label with b1-integrin, and are in close apposition to, mostly extracellular located, fibronectin. In grey matter lesions, TG2 positive microglia co-label with b1-integrin, but no fibronectin is present. For this study we were able to obtain material from marmosets suffering from EAE. This primate has high genetic similarity to humans. Its mature immune system, shaped by life-long exposure to environmental and latent infections, resembles the human immune system. The MS-like disease phenotype and pathology of marmoset EAE is therefore a useful model to investigate if certain factors, in this case TG2, contribute to the pathogenesis of MS.