Biology Reference
In-Depth Information
the anemia is in conjunction with an MPD, suggesting that myeloid
progenitors preferentially produce GM cells at the expense of RBCs in
such settings.
Deficiencies in WBCs such as B and T cells are also observed in the
absence of Dicer, as described above, and this impairs the immune response.
Individual miRNAs that regulate lymphocyte development have the pro-
pensity to perturb immune function and create an immunodeficiency. In
such cases, an inadequate immune response would lead to greater suscepti-
bility to infection. The interplay between the immune system and solid
tumors could also be impacted and might result in enhanced tumor growth.
Conversely, if the immune system develops inappropriately, it can
trigger responses against self-tissues. miRNAs have recently been linked
to a variety of autoimmune conditions, with their altered expression corre-
lating with disease (
Pauley
et al
., 2009
). The importance of miRNAs during
autoimmunity is demonstrated by the consequences of a lack of Dicer on
Tregs, impairing their development and unleashing a lethal autoimmune
condition. Among the specific miRNAs expressed in Tregs, genetic dele-
tion of miR-146a has been shown to impair Treg function resulting in
autoimmune inflammation (
Lu
et al
., 2010
). Furthermore, two recent
studies have found that a lack of miR-155 or inhibition of miR-326 in
mice can reduce symptoms of experimental autoimmune encephalomyeli-
tis, a model of human multiple sclerosis (
Du
et al
., 2009
;
O'Connell
et al
.,
2010b
). In both of these cases, a reduction in inflammatory T cell develop-
ment was observed.
6. Concluding Remarks
The studies described in this review indicate that hematopoietic
miRNAs commonly regulate certain types of cellular pathways
(
Table 6.2
). Some miRNAs, such as miR-155, miR-146a, miR-181a,
miR-126, miR-451, and miR-21, target proteins involved in cytokine,
TLR, or antigen receptor signaling pathways and consequently impact the
magnitude of the cellular response to ligands (
Li
et al
., 2007, 2008
;
Lu
et al
.,
2009
;
O'Connell
et al
., 2009
;
Patrick
et al
., 2010
;
Sheedy
et al
., 2009
;
Taganov
et al
., 2006
). Other miRNAs repress protein regulators of apopto-
sis and influence cell survival. These include the miR-125 family, miR-
15a/16-1, and miRs-17-92 (
Cimmino
et al
., 2005
;
Guo
et al
., 2010
;
Klein
et al
., 2010
;
Ooi
et al
., 2010
;
Xiao
et al
., 2008
). Several hematopoietic
miRNAs, including miR-150, miR-155, miR-29a, miR-146a, miR-34a,
miR-223, miR-196b, and miR-326, directly target transcription factors
that control lineage choice (
Du
et al
., 2009
;
Fabbri
et al
., 2007
;
Hu
et al
.,
2010
;
Johnnidis
et al
., 2008
;
Lu
et al
., 2010
;
Popovic
et al
., 2009
;
Rao
et al
.,
