Fever is a highly conserved response to infection or injury and benefits organism survival and the resolution of many infections. Emerging evidence suggests that fever-range thermal stress (38-40°C) plays an active role in directing migration of immune cells into secondary lymphoid organs or inflammatory sites.
However, whether and how fever can regulate the function of integrins, the key cell adhesion molecules in mediating immune cell trafficking, has remained obscure.
In a recent study published in Immunity, researchers demonstrated that fever promotes T lymphocyte trafficking through heat shock protein 90 (Hsp90)-induced α4 integrin activation and signaling in T cells.
By using T cells from mice, the scientists found that fever increased Hsp90 expression in T cells and promoted α4 integrin-mediated T cell adhesion and transmigration.
Hsp90 was found to bind to the α4 tail and activate α4 integrins via inside-out signaling. The N and C termini of one Hsp90 molecule were found to simultaneously bind to two α4 tails, leading to dimerization and clustering of α4 integrins on the cell membrane and subsequent activation of the FAK-RhoA pathway to promote T cell migration.
In addition, the scientists generated a knock-in mice line to disrupt Hsp90-α4 interaction in vivo and used several fever mouse models to study the biological function of the Hsp90-α4 integrin pathway.
They found abolishment of Hsp90-α4 interaction significantly inhibited fever-induced T cell trafficking to draining lymph nodes and impaired the clearance of Salmonella typhimurium infection.
These findings identified the Hsp90-α4 integrin axis as a novel thermal sensory pathway that promotes T cell trafficking and enhances immune surveillance during infection. In addition to T cells, this mechanism can apply to different immune cells expressing α4 integrins like monocytes and B cells, suggesting its general role in both innate and adaptive immune responses.
https://www.cell.com/immunity/fulltext/S1074-7613(18)30495-3?_
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Ffever-promotes-t&filter=22
Fever activates Hsp90-integrin pathway to traffic T-lymphocytes
- 2,175 views
- Added
Edited
Latest News
Wiring of the human neocortex
By newseditor
Posted 24 Apr
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Other Top Stories
Lipid nanoparticle-mRNA (LNP-mRNA) to treat liver failure
Read more
AI to predict cardiovascular risk
Read more
Aggravated multiple sclerosis from childhood trauma linked to beta-…
Read more
Common fronto-temporal effective connectivity in humans and monkeys
Read more
Reduced growth in boys with neonatal antibiotic use
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Harnessing gastrointestinal…
By newseditor
Posted 24 Apr
Sex-specific modulation of…
By newseditor
Posted 24 Apr
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar