1. INTRODUCTION
For decades, the central nervous system (CNS) has been considered an
immune-isolated organ, due to the lack of lymphatic vessels and the
restriction of the blood-brain barrier (BBB), which limits the access of
immune cells (Arcuri, Mecca, Giambanco & Donato, 2019; Mapunda, Tibar,
Regragui & Engelhardt, 2022). However, recent studies have shown
evidence of the presence of immune cells in both physiological and
pathological conditions within the CNS (Arcuri, Mecca, Giambanco &
Donato, 2019; Stephenson, Nutma, van der Valk & Amor, 2018). The use of
lymphatic-cell-reporter mice has demonstrated the existence of classic
lymphatic vessels within the layers of the meninges and the presence of
adaptive immune cells, such as T and B lymphocytes, in these vessels
under homeostatic conditions (Buckley & McGavern, 2022; Louveau et al.,
2015).
The meninges protect the brain and spinal cord and consist of three
different layers. The outermost layer, the dura mater, is a collagenous
membrane that is richly vascularized and innervated, and contains
numerous lymphatic vessels (Mapunda, Tibar, Regragui & Engelhardt,
2022; Rua & McGavern, 2018). The middle layer, the arachnoid mater,
primarily regulates molecules transport (Yasuda et al., 2013) and the
innermost layer, the pia mater, surrounds the parenchyma of the CNS.
Together, the arachnoid and pia maters are referred to as the
leptomeninges (Decimo, Fumagalli, Berton, Krampera & Bifari, 2012).
Between these two lies the subarachnoid space (SAS), composed of
trabeculae and collagen fibers. The cerebrospinal fluid (CSF), produced
by the ependymal cells of the choroid plexus (CP), flows through this
space (Rua & McGavern, 2018). The dural lymphatic vessels reabsorb the
CSF from the SAS through glymphatic system (Buckley & McGavern, 2022;
Prinz & Priller, 2017) (Figure 1).
Dysregulation of the CNS immune response can lead to the development of
autoimmune diseases, such as multiple sclerosis (MS) (Ransohoff, 2016).
A thorough comprehension of the role of T cells in this scenario, as
well as the molecular processes underlying age-related changes under
normal conditions, could provide new opportunities for research on
understanding the brain in autoimmune and neurodegenerative diseases.