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*
Department of Pediatric Immunology, Wilhelmina Children’s Hospital of the University Medical Center Utrecht, Utrecht, The Netherlands;
Department of Clinical Immunology, Hannover Medical School, Hannover, Germany; and
Institut für Medizinische Psychologie, Essen, Germany
G protein-coupled receptors (GPCR) play a crucial role in the
regulation of the immune response by, e.g., chemokines, PGs, and
2-adrenergic agonists. The responsiveness of these GPCRs
is turned off by the family of G protein-coupled receptor kinases
(GRK1–6). These kinases act by phosphorylating the GPCR in an
agonist-dependent manner, resulting in homologous desensitization of
the receptor. Although GRKs are widely expressed throughout the body,
leukocytes express relatively high levels of GRKs, in particular GRK2,
-3, and -6. We investigated whether in vivo the inflammatory disease
adjuvant arthritis (AA) induces changes in GRK expression and function
in the immune system. In addition, we analyzed whether the systemic
effects of AA also involve changes in GRKs in nonimmune organs. At the
peak of the inflammatory process, we observed a profound
down-regulation of GRK2, -3, and -6 in splenocytes and mesenteric lymph
node cells from AA rats. Interestingly, no changes in GRK were observed
in thymocytes and in nonimmune organs such as heart and pituitary.
During the remission phase of AA, GRK levels in spleen and mesenteric
lymph nodes are returning to baseline levels. The decrease in GRK2 at
the peak of AA is restricted to CD45RA+ B cells and
CD4+ T cells, and was not observed in CD8+ T
cells. In conclusion, we demonstrate in this study, for the first time,
that an inflammatory process in vivo induces a tissue-specific
down-regulation of GRKs in the immune system.
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