The subfornical organ is a nucleus for gut-derived T cells that regulate behaviour 2025 Wang et al

Abstract

Specialized immune cells that reside in tissues orchestrate diverse biological functions by communicating with parenchymal cells1. The contribution of the innate immune compartment in the meninges and the central nervous system (CNS) is well-characterized; however, whether cells of the adaptive immune system reside in the brain and are involved in maintaining homeostasis is unclear2,3,4.

Here we show that the subfornical organ (SFO) of the brain is a nucleus for parenchymal αβ T cells in the steady-state brain in both mice and humans. Using unbiased transcriptomics, we show that these extravascular T cells in the brain are distinct from meningeal T cells: they secrete IFNγ robustly and express tissue-residence proteins such as CXCR6, which are required for their retention in the brain and for normal adaptive behaviour. These T cells are primed in the periphery by the microbiome, and traffic from the white adipose and gastrointestinal tissues to the brain. Once established, their numbers can be modulated by alterations to either the gut microbiota or the composition of adipose tissue.

In summary, we find that CD4 T cells reside in the brain at steady state and are anatomically concentrated in the SFO in mice and humans; that they are transcriptionally and functionally distinct from meningeal T cells; and that they secrete IFNγ to maintain CNS homeostasis through homeostatic fat–brain and gut–brain axes.

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Perhaps it's the answer.
T cells in the brain.

 

Do we have drugs that directly or indirectly affect T cells in the brain?

 

No idea.

 

There's a reference to photo-staining t-cells from fat and then finding them in the brain. I think. Is this paper saying t-cells are travelling from the fat to the brain?

 

Additional research has demonstrated that the subfornical organ may be an important intermediary through which leptin acts to maintain blood pressure within normal physiological limits via descending autonomic pathways associated with cardiovascular control.



It must be the answer!

 

Can such a tiny bit in the brain mess up so much?