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response. Indeed, T cells from GRK2+/- mice, that display a 50% reduction
in GRK2 levels, showed a significant increase in signalling and chemotaxis
toward CCR1 and CCR5 receptor ligands compared to wild-type T cells
(22). However, whether GRK2 expression levels are determinant for the
progression of RA still requires further evidence. Interestingly, such notion
was indeed demonstrated for another inflammatory disorder, i.e. multiple
sclerosis (MS) (23). Expression of GRK2 in leukocytes from patients
suffering from MS, but not from neurological disorders without an
inflammatory component, was also decreased by circa 40% compared with
kinase levels from healthy individuals. GRK2 levels have a direct impact
in the clinical course of experimental MS. Thus, the onset of the relapsing-
remitting experimental autoimmune encephalomyelitis (EAE) in
hemizygous GRK2+/- mice was significantly accelerated, what is paralleled
by a higher initial infiltration of T cells into the brain. Curiously, these
animals display lower inflammatory infiltrates in the long-term and do not
develop relapses of the disease compared to wild-type animals. Reactive
microglia and neuronal damage secondary to excessive glutamate
signalling are important components of diverse neurological disorder that
course with inflammation. Interestingly, GRK2 expression levels in brain
also modulates the strength of microglia-mediated inflammation, what
might determine the sensitivity to cerebral stroke by means of rate-limiting
the extent of local release of inflammatory mediators that could attract T
cells (24). Therefore, the effects of altered GRK2 expression are far to be
clear-cut in terms of inflammation, since many different cell types, not
only from the immune system but also from the inflamed tissue, are
responsible for the course of the disease and can respond distinctly to
GRK2 changes.

Brain GRK2 also modulates the strength of microglia-mediated
inflammation and its protein expression levels might determine the
sensitivity to cerebral stroke (24). Reactive microglia and neuronal damage
secondary to excessive glutamate signalling are important components of
AD pathology. Recently, a study aimed to evaluate peripheral lymphocyte
GRK2 expression in patients suffering from AD has shown a positive
correlation between kinase protein levels and the severity of the disease
(25).

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