scholarly journals T?cell homeostasis requires G?protein-coupled receptor-mediated access to trophic signals that promote growth and inhibit chemotaxis

2005 ◽  
Vol 35 (3) ◽  
pp. 786-795 ◽  
Author(s):  
Ryan?M. Cinalli ◽  
Catherine?E. Herman ◽  
Brian?O. Lew ◽  
Heather?L. Wieman ◽  
Craig?B. Thompson ◽  
...  
Keyword(s):  
T Cell ◽  
G Protein ◽  
T Cell Homeostasis ◽  
G Protein Coupled Receptor ◽  
Cell Homeostasis ◽  
G Protein Coupled

scholarly journals G Protein-Coupled Receptor Kinase 2 (GRK2) Regulates T Cell Response in a Murine Model of House Dust Mite-Induced Asthma

2021 ◽  
Vol 2 ◽  
Author(s):  
Ananth K. Kammala ◽  
Canchai Yang ◽  
Reynold A. Panettieri ◽  
Rupali Das ◽  
Hariharan Subramanian
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
G Protein ◽  
House Dust ◽  
House Dust Mite ◽  
T Cell Response ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Dust Mite ◽  
G Protein Coupled

G protein-coupled receptor kinase 2 (GRK2) is an adapter protein that modulates G protein-coupled receptor (GPCR) signaling. It also regulates the functions and activity of other intracellular proteins in many cell types. Accordingly, GRK2 is thought to contribute to disease progression by a variety of mechanisms related to its multifunctional roles. Indeed, GRK2 levels are enhanced in patient samples as well as in preclinical models of several diseases. We have previously shown that GRK2 regulates mast cell functions, and thereby contributes to exacerbated inflammation during allergic reactions. In the current study, we observed that GRK2 levels are enhanced in the lungs of human asthma patients and in mice sensitized to house dust mite extract (HDME) allergen. Consistent with these findings, interleukin (IL)-4 and IL-13 levels were reduced in the lungs of GRK2+/− mice in a HMDE mouse model of asthma. Because Th2 cells are the major source of these cytokines during asthma, we determined the role of GRK2 in regulating T cell-specific responses in our HMDE mouse model. We observed a significant reduction of airway hyperresponsiveness (AHR), lung eosinophil and lymphocyte counts, serum IgE, Th2 cytokines (IL-4 and IL-13), goblet cell hyperplasia and mucus production in mice that had reduced GRK2 expression specifically in T cells. Collectively, our studies reveal an important role for GRK2 in regulating T cell response during asthma pathogenesis and further elucidation of the mechanisms through which GRK2 modulates airway inflammation will lead to the development of new therapeutic strategies for asthma.

scholarly journals A T-cell–redirecting bispecific G-protein–coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma

Blood ◽  
2020 ◽  
Vol 135 (15) ◽  
pp. 1232-1243 ◽  
Author(s):  
Kodandaram Pillarisetti ◽  
Suzanne Edavettal ◽  
Mark Mendonça ◽  
Yingzhe Li ◽  
Mark Tornetta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
G Protein ◽  
T Cell Activation ◽  
Cell Activation ◽  
Plasma Cells ◽  
Phase 1 ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Abstract T-cell–mediated approaches have shown promise in myeloma treatment. However, there are currently a limited number of specific myeloma antigens that can be targeted, and multiple myeloma (MM) remains an incurable disease. G-protein–coupled receptor class 5 member D (GPRC5D) is expressed in MM and smoldering MM patient plasma cells. Here, we demonstrate that GPRC5D protein is present on the surface of MM cells and describe JNJ-64407564, a GPRC5DxCD3 bispecific antibody that recruits CD3+ T cells to GPRC5D+ MM cells and induces killing of GPRC5D+ cells. In vitro, JNJ-64407564 induced specific cytotoxicity of GPRC5D+ cells with concomitant T-cell activation and also killed plasma cells in MM patient samples ex vivo. JNJ-64407564 can recruit T cells and induce tumor regression in GPRC5D+ MM murine models, which coincide with T-cell infiltration at the tumor site. This antibody is also able to induce cytotoxicity of patient primary MM cells from bone marrow, which is the natural site of this disease. GPRC5D is a promising surface antigen for MM immunotherapy, and JNJ-64407564 is currently being evaluated in a phase 1 clinical trial in patients with relapsed or refractory MM (NCT03399799).

scholarly journals Transduction of Multiple Effects of Sphingosine 1-Phosphate (S1P) on T Cell Functions by the S1P1 G Protein-Coupled Receptor

2003 ◽  
Vol 171 (7) ◽  
pp. 3500-3507 ◽  
Author(s):  
Glenn Dorsam ◽  
Markus H. Graeler ◽  
Christine Seroogy ◽  
Yvonne Kong ◽  
Julia K. Voice ◽  
...  
Keyword(s):  
T Cell ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Cell Functions ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

scholarly journals JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

Leukemia ◽  
2016 ◽  
Vol 30 (6) ◽  
pp. 1311-1319 ◽  
Author(s):  
M-L Nairismägi ◽  
J Tan ◽  
J Q Lim ◽  
S Nagarajan ◽  
C C Y Ng ◽  
...  
Keyword(s):  
T Cell ◽  
Signaling Pathways ◽  
G Protein ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Receptor Signaling ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled
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