Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism.
Fever is an evolutionarily conserved response during acute inflammation, although its physiological benefit is poorly understood. Here we show thermal stress in the range of fever temperatures increased the intravascular display of two 'gatekeeper' homing molecules, intercellular adhesion molecule 1 (ICAM-1) and CCL21 chemokine, exclusively in high endothelial venules (HEVs) that are chief portals for the entry of blood-borne lymphocytes into lymphoid organs. Enhanced endothelial expression of ICAM-1 and CCL21 was linked to increased lymphocyte trafficking across HEVs. A bifurcation in the mechanisms controlling HEV adhesion was demonstrated by evidence that the thermal induction of ICAM-1 but not of CCL21 involved an interleukin 6 trans-signaling pathway. Our findings identify the 'HEV axis' as a thermally sensitive alert system that heightens immune surveillance during inflammation by amplifying lymphocyte trafficking to lymphoid organs.
Chen
Qing
Q
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Fisher
Daniel T
DT
Clancy
Kristen A
KA
Gauguet
Jean-Marc M
JM
Wang
Wan-Chao
WC
Unger
Emily
E
Rose-John
Stefan
S
von Andrian
Ulrich H
UH
Baumann
Heinz
H
Evans
Sharon S
SS
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005334:Fever / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000098:blood supply / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D015398:Signal Transduction / Q000276:immunology*; D013312:Stress, Physiological / Q000276:immunology / Q000378:metabolism; D014699:Venules / Q000276:immunology / Q000378:metabolism
C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1