PMID- 33952618
OWN - NLM
STAT- MEDLINE
DCOM- 20210917
LR  - 20220516
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 206
IP  - 10
DP  - 2021 May 15
TI  - Na(+)/H(+) Exchanger Regulatory Factor 1 Mediates the Pathogenesis of Airway 
      Inflammation in a Murine Model of House Dust Mite-Induced Asthma.
PG  - 2301-2311
LID - 10.4049/jimmunol.2001199 [doi]
AB  - Na(+)/H(+) exchanger regulatory factor 1 (NHERF1), a class I PDZ-binding protein, 
      regulates G protein-coupled receptor signaling in some cell types. NHERF1 also 
      functions as a scaffolding protein and activates non-G protein-coupled receptor 
      signaling pathways, thereby contributing to the pathogenesis of various diseases. 
      Although we have previously shown that NHERF1 regulates mast cell functions, 
      there is little information regarding the role of NHERF1 in other immune cells. 
      How NHERF1 regulates the pathogenesis of allergic disease such as asthma also 
      remains unknown. In the current study, we show that NHERF1 promotes allergic 
      airway inflammation in a house dust mite extract (HDME)-induced mouse model of 
      asthma. Specifically, HDME-specific serum IgE levels, airway leukocyte numbers, 
      and goblet cell hyperplasia were reduced in NHERF1(+/-) mice as compared with 
      NHERF1(+/+) mice. Interestingly, the gene expression of inflammatory (IL-17a, 
      IL-25, and IL-33) as well as T helper 2 (Th2) cytokines (IL-4, IL-5, and IL-13) 
      and several chemokines that recruit eosinophils, neutrophils, and lymphocytes 
      were also decreased in the lungs of NHERF1(+/-) mice exposed to HDME. Consistent 
      with these observations, microRNAs regulating mucus production, inflammation, Th2 
      effector functions, and IL-13 expression were increased in the lungs of 
      HDME-treated NHERF1(+/-) mice. Overall, our studies reveal a unique role for 
      NHERF1 in regulating asthma pathogenesis, and further elucidation of the 
      mechanisms through which NHERF1 modulates allergic inflammation will lead to the 
      development of new therapeutic strategies for asthma.
CI  - Copyright (c) 2021 by The American Association of Immunologists, Inc.
FAU - Kammala, Ananth K
AU  - Kammala AK
AD  - Department of Physiology, Michigan State University, East Lansing, MI.
FAU - Bahal, Devika
AU  - Bahal D
AD  - Department of Physiology, Michigan State University, East Lansing, MI.
FAU - Yang, Canchai
AU  - Yang C
AUID- ORCID: 0000-0002-0125-9298
AD  - Department of Physiology, Michigan State University, East Lansing, MI.
FAU - Panettieri, Reynold A Jr
AU  - Panettieri RA Jr
AUID- ORCID: 0000-0003-0834-4636
AD  - Rutgers Institute for Translational Medicine and Science, New Brunswick, NJ.
FAU - Das, Rupali
AU  - Das R
AD  - Department of Physiology, Michigan State University, East Lansing, MI 
      dasrupal@msu.edu subram46@msu.edu.
FAU - Subramanian, Hariharan
AU  - Subramanian H
AD  - Department of Physiology, Michigan State University, East Lansing, MI 
      dasrupal@msu.edu subram46@msu.edu.
LA  - eng
GR  - P01 HL114471/HL/NHLBI NIH HHS/United States
GR  - K22CA18814802/NH/NIH HHS/United States
GR  - R00 HL121073/HL/NHLBI NIH HHS/United States
GR  - 5R00HL12107305/NH/NIH HHS/United States
GR  - K22 CA188149/CA/NCI NIH HHS/United States
GR  - UL1 TR003017/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210505
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cytokines)
RN  - 0 (Phosphoproteins)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - 0 (sodium-hydrogen exchanger regulatory factor)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Asthma/*blood/genetics/*immunology/pathology
MH  - Case-Control Studies
MH  - Cytokines/genetics/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression
MH  - Goblet Cells/pathology
MH  - Humans
MH  - Hyperplasia
MH  - Immunoglobulin E/blood/immunology
MH  - Inflammation/immunology
MH  - Lung/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Middle Aged
MH  - Phosphoproteins/genetics/*metabolism
MH  - Pyroglyphidae/*immunology
MH  - Sodium-Hydrogen Exchangers/genetics/*metabolism
MH  - Young Adult
PMC - PMC8113128
MID - NIHMS1685561
COIS- CONFLICT OF INTEREST The authors have no conflict of interest to declare.
EDAT- 2021/05/07 06:00
MHDA- 2021/09/18 06:00
PMCR- 2022/05/15
CRDT- 2021/05/06 05:55
PHST- 2020/10/22 00:00 [received]
PHST- 2021/03/16 00:00 [accepted]
PHST- 2021/05/07 06:00 [pubmed]
PHST- 2021/09/18 06:00 [medline]
PHST- 2021/05/06 05:55 [entrez]
PHST- 2022/05/15 00:00 [pmc-release]
AID - jimmunol.2001199 [pii]
AID - 10.4049/jimmunol.2001199 [doi]
PST - ppublish
SO  - J Immunol. 2021 May 15;206(10):2301-2311. doi: 10.4049/jimmunol.2001199. Epub 
      2021 May 5.