PMID- 35386975
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240512
IS  - 2673-6101 (Electronic)
IS  - 2673-6101 (Print)
IS  - 2673-6101 (Linking)
VI  - 2
DP  - 2021
TI  - G Protein-Coupled Receptor Kinase 2 (GRK2) Regulates T Cell Response in a Murine 
      Model of House Dust Mite-Induced Asthma.
PG  - 656886
LID - 10.3389/falgy.2021.656886 [doi]
LID - 656886
AB  - 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.
CI  - Copyright (c) 2021 Kammala, Yang, Panettieri, Das and Subramanian.
FAU - Kammala, Ananth K
AU  - Kammala AK
AD  - Department of Physiology, Michigan State University, East Lansing, MI, United 
      States.
FAU - Yang, Canchai
AU  - Yang C
AD  - Department of Physiology, Michigan State University, East Lansing, MI, United 
      States.
FAU - Panettieri, Reynold A
AU  - Panettieri RA
AD  - Rutgers Institute for Translational Medicine and Science, New Brunswick, NJ, 
      United States.
FAU - Das, Rupali
AU  - Das R
AD  - Department of Physiology, Michigan State University, East Lansing, MI, United 
      States.
FAU - Subramanian, Hariharan
AU  - Subramanian H
AD  - Department of Physiology, Michigan State University, East Lansing, MI, United 
      States.
LA  - eng
GR  - P01 HL114471/HL/NHLBI NIH HHS/United States
GR  - UL1 TR003017/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20210517
PL  - Switzerland
TA  - Front Allergy
JT  - Frontiers in allergy
JID - 9918227355906676
PMC - PMC8974720
OTO - NOTNLM
OT  - G protein-coupled receptor kinase 2
OT  - GRK2
OT  - airway hyperresponsiveness
OT  - airway inflammation
OT  - allergic diseases
OT  - asthma
OT  - goblet cell hyperplasia
OT  - house dust mite extract
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/08 06:00
MHDA- 2022/04/08 06:01
PMCR- 2021/05/17
CRDT- 2022/04/07 05:19
PHST- 2021/01/29 00:00 [received]
PHST- 2021/04/21 00:00 [accepted]
PHST- 2022/04/07 05:19 [entrez]
PHST- 2022/04/08 06:00 [pubmed]
PHST- 2022/04/08 06:01 [medline]
PHST- 2021/05/17 00:00 [pmc-release]
AID - 10.3389/falgy.2021.656886 [doi]
PST - epublish
SO  - Front Allergy. 2021 May 17;2:656886. doi: 10.3389/falgy.2021.656886. eCollection 
      2021.