Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Brain resident memory T cells rapidly expand and initiate neuroinflammatory responses following CNS injury and viral infection The contribution of circulating verses tissue resident memory T cells (TRM) to clinical neuropathology is an enduring question due to a lack of mechanistic insights. The prevailing view is TRM cells are protective against pathogens in the brain. However, the extent antigen-specific TRM cells can induce neuropathology upon reactivation has not been determined. Using the described phenotype of TRMs, we found that brains of naive mice harbor populations of CD69+ CD103- T cells. Notably, numbers of CD69+ CD103- TRM cells rapidly increase following neurological insults of physical, cancerous, or viral origins. This TRM expansion precedes infiltration of virus specific CD8 T cells and is due to proliferation of T cells within the brain. In contrast, the CD69+ CD103+ TRMs in the brain are generated after the initial expansion of CD69+ CD103- cells following injury and are antigen-specific. We next evaluated the capacity of antigen-specific TRMs in the brain to induce significant neuroinflammation post virus clearance, including infiltration of inflammatory monocytes, activation of T cells in the brain, and significant blood brain barrier disruption. These neuroinflammatory events were induced by TRMs, as depletion of peripheral T cells or blocking T cell trafficking using FTY720 did not change the neuroinflammatory course. Reactivation of antigen-specific TRMs in the brain also induced profound lymphopenia within the blood compartment. We have therefore determined that antigen-specific TRMs can induce significant neuroinflammation, neuropathology, and peripheral immune suppression. Importantly, understanding functions of brain TRMs is crucial in investigating their role in neurodegenerative disorders, CNS cancers, and long-term complications associated with viral infections including COVID-19.

Graphical AbstractHealthy brain harbors populations of resident memory T cells (TRM). These TRM cells rapidly proliferate in response to CNS insults of various origins. Following clearance of the insult, populations of TRM cells in the brain decline, but an antigen-specific TRM subset remains within the brain. Antigen-specific reactivation of brain TRMs mediates neuroinflammatory sequalae involving activation and blasting of resident T cells, infiltration of inflammatory monocytes and blood brain barrier disruption. Severe neuroinflammation within the brain following antigen-specific TRM reactivation is concurrent with profound lymphopenia within the blood compartment.

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/487707v1_ufig1.gif" ALT="Figure 1">
View larger version (44K):
org.highwire.dtl.DTLVardef@a22867org.highwire.dtl.DTLVardef@a90e0org.highwire.dtl.DTLVardef@1ad904eorg.highwire.dtl.DTLVardef@1dd281c_HPS_FORMAT_FIGEXP  M_FIG C_FIG
27
The categories of this paper are: pathology
28
The categories of this paper are: communication
14
The categories of this paper are: biophysics
13
The categories of this paper are: animal
4
The categories of this paper are: neuroscience
22
The categories of this paper are: physiology
29
The categories of this paper are: education
2
The categories of this paper are: biology
18
The categories of this paper are: systems
21
The categories of this paper are: toxicology
20
The categories of this paper are: pharmacology
30
The categories of this paper are: scientific
0
The categories of this paper are: genetics
10
The categories of this paper are: and
8
The categories of this paper are: genomics
32
The categories of this paper are: zoology