We read the interesting paper by Dr. Tong and colleagues (1) on the role of acid-sensing ion channels (ASICs) in the maturation of dendritic cells (DCs) induced by acidosis. The study sought understanding of the molecular mechanisms by which DCs detect changes in extracellular pH in a sensitive manner (2, 3).

The importance of acid–base homeostasis in the maintenance of normal cellular responses and physiological integrity has long been recognized. It is well known that extracellular acidosis improves the Ag-presenting capacity of DCs (4, 5). So far, however, few studies have noticed that some proteins could function as extracellular pH sensors in DCs. Interestingly, ASICs represent a novel class of ligand-gated cation channels that are activated by acidification and implicated in pain perception, ischemia, and rheumatoid arthritis (69). Tong et al. (1) first reported the potential role of ASICs in the physiological function of DCs as sensors for extracellular acidosis; they found that ASIC1, ASIC2, and ASIC3 were shown in mouse bone marrow-derived DCs, and the pH-dependent activation of ASIC currents in DCs was recorded. Moreover, their study data show that extracellular acidosis enhances the Ag-presenting ability of DCs via ASICs.

Collectively, the results provide us with a novel targeted molecule for sensing changes in extracellular acidosis in DCs. The study also yields a clue about other acid-sensitive proteins, such as transient receptor potential vanilloid-1 (TRPV1) ion channels, two-pore-domain K+ (K2P) channels, and G-protein–coupled receptors, which likely play some role in the acidosis-mediated effect on DC function.

1
Tong
J.
,
Wu
W. N.
,
Kong
X.
,
Wu
P. F.
,
Tian
L.
,
Du
W.
,
Fang
M.
,
Zheng
F.
,
Chen
J. G.
,
Tan
Z.
,
Gong
F.
.
2011
.
Acid-sensing ion channels contribute to the effect of acidosis on the function of dendritic cells.
J. Immunol.
186
:
3686
3692
.
2
Vermeulen
M.
,
Giordano
M.
,
Trevani
A. S.
,
Sedlik
C.
,
Gamberale
R.
,
Fernández-Calotti
P.
,
Salamone
G.
,
Raiden
S.
,
Sanjurjo
J.
,
Geffner
J. R.
.
2004
.
Acidosis improves uptake of antigens and MHC class I-restricted presentation by dendritic cells.
J. Immunol.
172
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3
Lardner
A.
2001
.
The effects of extracellular pH on immune function.
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4
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D.
,
Vermeulen
M.
,
von Euw
E.
,
Sabatté
J.
,
Maggíni
J.
,
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A.
,
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A.
,
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K.
,
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G.
,
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M.
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2007
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Extracellular acidosis triggers the maturation of human dendritic cells and the production of IL-12.
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179
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5
Kellum
J. A.
,
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M.
,
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J.
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2004
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Science review: extracellular acidosis and the immune response: clinical and physiologic implications.
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T. L.
,
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Z. G.
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2007
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Dynamic regulation of acid-sensing ion channels by extracellular and intracellular modulators.
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7
Xiong
Z. G.
,
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X. M.
,
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X. P.
,
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M.
,
Hey
J.
,
Wei
W. L.
,
MacDonald
J. F.
,
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J. A.
,
Price
M. P.
,
Welsh
M. J.
,
Simon
R. P.
.
2004
.
Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.
Cell
118
:
687
698
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8
Yuan
F. L.
,
Chen
F. H.
,
Lu
W. G.
,
Li
X.
,
Li
J. P.
,
Li
C. W.
,
Xu
R. S.
,
Wu
F. R.
,
Hu
W.
,
Zhang
T. Y.
.
2010
.
Inhibition of acid-sensing ion channels in articular chondrocytes by amiloride attenuates articular cartilage destruction in rats with adjuvant arthritis.
Inflamm. Res.
59
:
939
947
.
9
Yuan
F. L.
,
Chen
F. H.
,
Lu
W. G.
,
Li
X.
,
Wu
F. R.
,
Li
J. P.
,
Li
C. W.
,
Wang
Y.
,
Zhang
T. Y.
,
Hu
W.
.
2010
.
Acid-sensing ion channel 1a mediates acid-induced increases in intracellular calcium in rat articular chondrocytes.
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340
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159
.