scholarly journals Cutting Edge: Regulator of G Protein Signaling-1 Selectively Regulates Gut T Cell Trafficking and Colitic Potential

2011 ◽  
Vol 187 (5) ◽  
pp. 2067-2071 ◽  
Author(s):  
Deena L. Gibbons ◽  
Lucie Abeler-Dörner ◽  
Tim Raine ◽  
Il-Young Hwang ◽  
Anett Jandke ◽  
...  
Keyword(s):  
T Cell ◽  
G Protein ◽  
Cutting Edge ◽  
G Protein Signaling ◽  
Cell Trafficking ◽  
Protein Signaling ◽  
T Cell Trafficking

scholarly journals Gα13 Mediates a Signal That Is Essential for Proliferation and Survival of Thymocyte Progenitors

2004 ◽  
Vol 200 (10) ◽  
pp. 1315-1324 ◽  
Author(s):  
V. McNeil Coffield ◽  
Whitney S. Helms ◽  
Qi Jiang ◽  
Lishan Su
Keyword(s):  
T Cell ◽  
Progenitor Cells ◽  
G Protein ◽  
Cell Receptor ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Organ Cultures ◽  
Fetal Thymus ◽  
Thymocyte Proliferation ◽  
Signaling Domain

G protein signaling via the Gα12 family (Gα12 and Gα13) has not been well studied in T cells. To investigate whether Gα12 and Gα13 are involved in thymopoiesis, we expressed the regulator of G protein signaling domain of p115RhoGEF to inhibit Gα12 and Gα13 during thymopoiesis. Fetal thymus organ cultures seeded with p115ΔDH-expressing progenitor cells showed impaired thymopoiesis with a block at the CD4−CD8−CD44−CD25+ (DN3) stage. Using Gα13 or Gα12 minigenes, we demonstrated that Gα13, but not Gα12, is required for thymopoiesis. T progenitor cells expressing p115ΔDH showed reduced proliferation and increased cell death. T cell receptor stimulation of the fetal thymus organ cultures did not rescue the block. Overexpression of the antiapoptotic gene Bcl2 rescued the defect in DN3 cells and partially rescued T cell development. Therefore, Gα13-mediated signaling is necessary in early thymocyte proliferation and survival.

scholarly journals RGS3 controls T lymphocyte migration in a model of Th2-mediated airway inflammation

2013 ◽  
Vol 305 (10) ◽  
pp. L693-L701 ◽  
Author(s):  
Jesse W. Williams ◽  
Douglas Yau ◽  
Nan Sethakorn ◽  
Jacob Kach ◽  
Eleanor B. Reed ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Migration ◽  
T Cell ◽  
Immune Responses ◽  
G Protein ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Cell Numbers ◽  
T Cell Migration

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 (RGS3ΔRGS) were generated and tested in an experimental model of asthma. Compared with littermate controls, the inflammation in the RGS3ΔRGS 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 RGS3ΔRGS 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 RGS3ΔRGS, demonstrating a redistribution of T cells from the dLN to the lungs via increased RGS3ΔRGS 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.

scholarly journals Systematic Assessment of Chemokine Signaling at Chemokine Receptors CCR4, CCR7 and CCR10

2021 ◽  
Vol 22 (8) ◽  
pp. 4232
Author(s):  
Herman D. Lim ◽  
J. Robert Lane ◽  
Meritxell Canals ◽  
Martin J. Stone
Keyword(s):  
G Protein ◽  
Chemokine Receptors ◽  
Scavenger Receptor ◽  
G Protein Signaling ◽  
Cell Trafficking ◽  
Protein Signaling ◽  
Systematic Assessment ◽  
Biased Agonism ◽  
Cc Chemokine ◽  
Stimulation Of

Chemokines interact with chemokine receptors in a promiscuous network, such that each receptor can be activated by multiple chemokines. Moreover, different chemokines have been reported to preferentially activate different signalling pathways via the same receptor, a phenomenon known as biased agonism. The human CC chemokine receptors (CCRs) CCR4, CCR7 and CCR10 play important roles in T cell trafficking and have been reported to display biased agonism. To systematically characterize these effects, we analysed G protein- and β-arrestin-mediated signal transduction resulting from stimulation of these receptors by each of their cognate chemokine ligands within the same cellular background. Although the chemokines did not elicit ligand-biased agonism, the three receptors exhibited different arrays of signaling outcomes. Stimulation of CCR4 by either CC chemokine ligand 17 (CCL17) or CCL22 induced β-arrestin recruitment but not G protein-mediated signaling, suggesting that CCR4 has the potential to act as a scavenger receptor. At CCR7, both CCL19 and CCL21 stimulated G protein signaling and β-arrestin recruitment, with CCL19 consistently displaying higher potency. At CCR10, CCL27 and CCL28(4-108) stimulated both G protein signaling and β-arrestin recruitment, whereas CCL28(1-108) was inactive, suggesting that CCL28(4-108) is the biologically relevant form of this chemokine. These comparisons emphasize the intrinsic abilities of different receptors to couple with different downstream signaling pathways. Comparison of these results with previous studies indicates that differential agonism at these receptors may be highly dependent on the cellular context.

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