b-Arrestins in the Immune System - Progress in Molecular Biology and Translational Science - page 371

6.5. Encephalomyelitis
b -Arrestin protein expression was significantly increased in splenocytes
following myelin oligodendrocyte glycoprotein-induced experimental
autoimmune encephalomyelitis (EAE), while GRK2, GRK6, and A1 aden-
osine receptors were decreased during the disease. 157,158 Mice deficient in
b -arrestin 1 were more resistant to EAE, whereas overexpression of
b -arrestin 1 increased susceptibility to the disease. 46 Glucocorticoid treat-
ment eliminated EAE-induced neuroinflammation and neurobehavioral
deficits, and also reduced b -arrestin 1 expression and enhanced A1 adeno-
sine receptor expression. 157 These results suggest that b -arrestins may play a
pathogenic role in EAE.

6.6. Acute rejection in organ transplant
b -Arrestins 1 and 2 are expressed by intravascular renal graft monocytes and
T cells in a rat model of kidney transplantation, and b -arrestin 1 and 2
expression is decreased in monocytes during rejection. Decreased b -arrestin
2 expression was concurrent with depression of I- k B and augmentation of
NF- k B. 28 These data suggest that the upregulation of b -arrestin 2 in renal
isografts may suppress the activation of blood monocytes via NF- k B activa-
tion. Ischemic injury following heart transplantation reduced b -arrestin 1
expression. 159 The immunomodulatory peptide a -melanocyte-stimulating
hormone was able to preserve b -arrestin 1 protein levels 159

and reduced

damage in transplanted heart grafts.

6.7. Asthma
Asthma is characterized by chronic airway inflammation and airway hyper-
responsiveness. Studies have showed that Th2 cytokines such as IL-4 and
IL-13 play a key role in the pathogenesis. b -Arrestin 2 regulates T-cell func-
tion in human asthma and animal models of allergic asthma. b -Arrestin 2
knockout mice are protected from OVA-induced allergic asthmatic inflam-
mation, but not LPS-mediated nonallergic inflammation, suggesting that
neutrophil recruitment is not dependent on b -arrestin 2. b -Arrestin 2-
deficient mice are competent in their ability to present antigen, to generate
antigen-specific T-cell responses, and to undergo Ig isotype switching, but
they have defective macrophage-derived chemokine-mediated CD4 þ
T lymphocytes migration to sites of inflammation. 55 A subsequent study
determined the cell types required for

b -arrestin 2-dependent allergic