CCR2 regulates monocyte recruitment as well as CD4 T1 allorecognition after lung transplantation.
Graft rejection remains a formidable problem contributing to poor outcomes after lung transplantation. Blocking chemokine pathways have yielded promising results in some organ transplant systems. Previous clinical studies have demonstrated upregulation of CCR2 ligands following lung transplantation. Moreover, lung injury is attenuated in CCR2-deficient mice in several inflammatory models. In this study, we examined the role of CCR2 in monocyte recruitment and alloimmune responses in a mouse model of vascularized orthotopic lung transplantation. The CCR2 ligand MCP-1 is upregulated in serum and allografts following lung transplantation. CCR2 is critical for the mobilization of monocytes from the bone marrow into the bloodstream and for the accumulation of CD11c(+) cells within lung allografts. A portion of graft-infiltrating recipient CD11c(+) cells expresses both recipient and donor MHC molecules. Two-photon imaging demonstrates that recipient CD11c(+) cells are associated with recipient T cells within the graft. While recipient CCR2 deficiency does not prevent acute lung rejection and is associated with increased graft infiltration by T cells, it significantly reduces CD4(+) T(h)1 indirect and direct allorecognition. Thus, CCR2 may be a potential target to attenuate alloimmune responses after lung transplantation.
Gelman
A E
AE
Department of Surgery, Washington University in St Louis, St Louis, MO, USA.
Okazaki
M
M
Sugimoto
S
S
Li
W
W
Kornfeld
C G
CG
Lai
J
J
Richardson
S B
SB
Kreisel
F H
FH
Huang
H J
HJ
Tietjens
J R
JR
Zinselmeyer
B H
BH
Patterson
G A
GA
Miller
M J
MJ
Krupnick
A S
AS
Kreisel
D
D
D000818:Animals; D018925:Chemokines; D006084:Graft Rejection / Q000276:immunology; D007249:Inflammation; D016040:Lung Transplantation / Q000379:methods*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D011014:Pneumonia / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014184:Transplantation, Homologous
D018925:Chemokines