depression and immune response

An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects. The research, published Sept. 18 in the journal Science Immunology, suggests these immune cells may play a role other than protecting against microbial invaders—protecting our mental health.

The results buttress an emerging theory that gamma interferons, a type of immune cell that helps induce and modulate a variety of immune system responses, may also play a role in preventing depression in healthy people.

Previous research has shown that blocking gamma interferons and the T cells they help produce can cause depression-like symptoms in mice. Hafler notes that depression is also a common side effect in patients with MS treated with a different type of interferon.

 

논문 intro

The central nervous system (CNS) contains a unique immunological state, as the blood-brain and blood–cerebrospinal fluid (CSF) barriers exclude most peripheral cells to prevent damaging inflammation (1). However, pathogens are able to enter and damage the CNS, necessitating persistent immune surveillance. A major route for this surveillance is the CSF, which is predominantly composed of T cells whose trafficking involves the 41 integrin (1) and the T helper 1 (TH1)–associated chemokine receptor CXCR3 (2). T cells in the CNS are critical for the control of a range of pathogens in the CNS (3, 4). Disrupting T cell entry to the CNS can predispose individuals to the development of lethal infections, for example, by the JC polyomavirus after treatment with the 4 integrin binding antibody natalizumab (5). T cells have been shown to persist in the brain of mice after viral infection and adopt characteristics of tissue-resident memory T (TRM) cells, which may provide a way for T cells to be poised to respond to reinfection at the tissue site (6). However, in addition to their critical role in protecting the CNS from pathogens, peripheral immune cells that enter the CNS can also drive neuroinflammation (7). The CSF provides insight into the state of the human CNS, as cellular, metabolic, and protein content can be reflective of a range of neurological diseases (8–11). In multiple sclerosis (MS), evidence of immune activation in the CSF, including antibodies made from clonally expanded B cells, is common metrics for diagnosis (12), and there is sharing of T and B cell populations between the brain parenchyma and CSF in MS (13, 14). These characteristics make the CSF a valuable way to assess immune function in the CNS in health and disease.

 

reference

J.L. Pappalardo el al., "Transcriptomic and clonal characterization of T cells in the human central nervous system," Science Immunology (2020). immunology.sciencemag.org/look … 6/sciimmunol.abb8786