The immune system in neurological diseases: What innate-like T cells have to say

The immune system classically consists of 2 lines of defense, innate and adaptive, both of which interact with one another effectively to protect us against any pathogenic threats. Importantly, there is a diverse subset of cells known as innatelike T cells that act as a bridge between the innate and adaptive immune systems and are pivotal players in eliciting inflammatory immune responses. A growing body of evidence has demonstrated the regulatory impact of these innate -like T cells in central nervous system (CNS) diseases and that such immune cells can traffic into the brain in multiple pathological conditions, which can be typically attributed to the breakdown of the blood -brain barrier. However, until now, it has been poorly understood whether innate -like T cells have direct protective or causative properties, particularly in CNS diseases. Therefore, in this review, our attention is focused on discussing the critical roles of 3 unique subsets of unconventional T cells, namely, natural killer T cells, gd T cells, and mucosal-associated invariant T cells, in the context of CNS diseases, disorders, and injuries and how the interplay of these immune cells modulates CNS pathology, in an attempt to gain a better understanding of their complex functions. (J Allergy Clin Immunol 2024;153:91323.)