We read with interest the article by Srivastava et al. (1), which provides encouraging data on the role of IL-3 in rheumatoid arthritis (RA) by expanding regulatory T (Treg) cells. We suggest that effective targeting of Treg cells offers IL-3 a promising novel role in preventing arthritic bone destruction.

Bone destruction in RA is caused, in part, by the enhanced activity of osteoclasts (2). It is well known that Treg cells can inhibit osteoclast formation (3). The researchers have previously reported that IL-3 inhibits osteoclast formation induced by RANKL or TNF-α (4, 5), but the exact mechanisms of IL-3 in bone resorption remain unclear until now. Interestingly, Srivastava et al. (1) provide the first report that IL-3 strikingly reduces inflammation and protects bone loss in collagen-induced arthritic mice by modulating the development of Treg cells. Meanwhile, the data showed that IL-3 induces development of Treg cells indirectly through secretion of IL-2.

Collectively, these observations suggest that IL-3 treatment could be used to control bone destruction in arthritis by increasing the percentage of Treg cells. Further studies are required, especially in human systems, to comprehensively explore the role of IL-3 in modulating Treg cell development in RA patients. Thus, understanding the function of IL-3 in Treg cell-mediated osteoclast suppression could result in important innovative therapies for bone destruction in RA.

1
Srivastava
R. K.
,
Tomar
G. B.
,
Barhanpurkar
A. P.
,
Gupta
N.
,
Pote
S. T.
,
Mishra
G. C.
,
Wani
M. R.
.
2011
.
IL-3 attenuates collagen-induced arthritis by modulating the development of Foxp3+ regulatory T cells
.
J. Immunol.
186
:
2262
2272
.
2
Pöllinger
B.
,
Junt
T.
,
Metzler
B.
,
Walker
U. A.
,
Tyndall
A.
,
Allard
C.
,
Bay
S.
,
Keller
R.
,
Raulf
F.
,
Di Padova
F.
, et al
.
2011
.
Th17 cells, not IL-17+ γδ T cells, drive arthritic bone destruction in mice and humans
.
J. Immunol.
186
:
2602
2612
.
3
Yuan
F. L.
,
Li
X.
,
Lu
W. G.
,
Xu
R. S.
,
Zhao
Y. Q.
,
Li
C. W.
,
Li
J. P.
,
Chen
F. H.
.
2010
.
Regulatory T cells as a potent target for controlling bone loss
.
Biochem. Biophys. Res. Commun.
402
:
173
176
.
4
Khapli
S. M.
,
Mangashetti
L. S.
,
Yogesha
S. D.
,
Wani
M. R.
.
2003
.
IL-3 acts directly on osteoclast precursors and irreversibly inhibits receptor activator of NF-kappa B ligand-induced osteoclast differentiation by diverting the cells to macrophage lineage
.
J. Immunol.
171
:
142
151
.
5
Yogesha
S. D.
,
Khapli
S. M.
,
Wani
M. R.
.
2005
.
Interleukin-3 and granulocyte-macrophage colony-stimulating factor inhibits tumor necrosis factor (TNF)-alpha-induced osteoclast differentiation by down-regulation of expression of TNF receptors 1 and 2
.
J. Biol. Chem.
280
:
11759
11769
.