RGS3 controls T lymphocyte migration in a model of Th2-mediated airway inflammation.
T cell migration toward sites of antigen exposure is mediated by G protein signaling and is a key function in the development of immune responses. Regulators of G protein signaling (RGS) proteins modulate G protein signaling; however, their role in the regulation of adaptive immune responses has not been thoroughly explored. Herein we demonstrated abundant expression of the Gi/Gq-specific RGS3 in activated T cells, and that diminished RGS3 expression in a T cell thymoma increased cytokine-induced migration. To examine the role of endogenous RGS3 in vivo, mice deficient in the RGS domain (RGS3(ΔRGS)) were generated and tested in an experimental model of asthma. Compared with littermate controls, the inflammation in the RGS3(ΔRGS) mice was characterized by increased T cell numbers and the striking development of perivascular lymphoid structures. Surprisingly, while innate inflammatory cells were also increased in the lungs of RGS3(ΔRGS) mice, eosinophil numbers and Th2 cytokine production were equivalent to control mice. In contrast, T cell numbers in the draining lymph nodes (dLN) were reduced in the RGS3(ΔRGS), demonstrating a redistribution of T cells from the dLN to the lungs via increased RGS3(ΔRGS) T cell migration. Together these novel findings show a nonredundant role for endogenous RGS3 in controlling T cell migration in vitro and in an in vivo model of inflammation.
Section of Pulmonary and Critical Care, Dept. of Medicine, The Univ. of Chicago, 5841 S. Maryland Ave., MC6076, Rm. M-648, Chicago, IL 60637. ndulin@medicine.bsd.uchicago.edu.
Jesse W
JW
Williams
Douglas
D
Yau
Nan
N
Sethakorn
Jacob
J
Kach
Eleanor B
EB
Reed
Tamson V
TV
Moore
Judy
J
Cannon
Xiaohua
X
Jin
Heming
H
Xing
Anthony J
AJ
Muslin
Anne I
AI
Sperling
Nickolai O
NO
Dulin
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000472:pathogenicity; D020710:RGS Proteins / Q000502:physiology*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D020710:RGS Proteins; C415085:Rgs3 protein, mouse
C cell; G proteins; T cell; asthma; regulators of G protein signaling