Abstract
While conducting numerous studies, including researchers in our laboratory, it was found that Th1/Th2 balance plays an essential role in the regulation of reactions that determine the outcomes of immunopathological processes in both chronic and acute GVHD models. However, the question about activity of which element in the regulatory process during GVHD induction (for example, a receptor or an enzyme) affects the ratio of this balance depends remains open. It has been suggested that the degree of activation of the GPR84 receptor during GVHD induction can significantly affect the host Th1/Th2 balance. And, by assessing this parameter, the direction of development and the intensity of the pathological process can be determined. The aim of this work was to investigate the effect of ligands such as medium-chain fatty acid receptor GPR84 on the Th1/Th2 balance in an experimental model in an in vivo system.Female DBA/2 and hybrids (C57Bl/6 × DBA/2) F1 mouse strains were used in the experiments.The studied ligands of GPR84 were capric and lauric acids, as well as a synthetic ligand 6-OAU. Chronic GVHD in the semi-allogenic system was induced by injecting splenocytes from DBA/2 mice to B6D2F1 hybrid mice: 60-70 × 106 -cells iv twice with an interval of 6 days. The first administration of the GPR84 ligands was performed one hour after the donor cell transfer and then once a day for two weeks.The effect of the study drugs on the course of chronic GVHD was assessed three months after the onset of the experiment.It was shown that the administration of GPR84 ligands to to animals during the induction of chronic GVHD affects the activity of the receptor and the host Th1/Th2 ratio. In the group with the injection of 6-OAU, the number of animals which the immunopathological process developed according to the Th1-dependent variant increased by more than 1.5-fold, compared with the control group. This fact is consistent with the literature data obtained in the in vitro system. Apparently, the effect of a mixture of capric and lauric acids is mediated by some other mechanism, differed from the GPR84 activation. Therefore, further research is required to realize the promising possibility of adjusting immune responses by including certain fatty acids in the diet.
Highlights
In the organism of experimental animals, a balance between type 1 and type 2 T-helper cells plays a decisive role in developing the graft versus host reaction (GVHD) in the classical semi-allogenic system with adoptive transfer of lymphoid cells from one of the parental lines to hybrid mice of the first generation
Cell transfer from C57Bl/6 mice to hybrid (C57Bl/6 × DBA/2)F1 mice is accompanied by domi nance of Th1-lymphocytes in immune responses and development of acute GVHD with pronounced tissue destruction and mass death of recipient animals
If DBA/2 mice are used as donors, a different type of immune conflict develops in recipient mice: chronic GVHD with predominance of Th2dependent reactions, intense polyclonal activation of B-lymphocytes, overproduction of antibodies and development of immunocomplex glomerulonephritis in some animals
Summary
In the organism of experimental animals, a balance between type 1 and type 2 T-helper cells plays a decisive role in developing the graft versus host reaction (GVHD) in the classical semi-allogenic system with adoptive transfer of lymphoid cells from one of the parental lines to hybrid mice of the first generation. Cell transfer from C57Bl/6 mice to hybrid (C57Bl/6 × DBA/2)F1 mice is accompanied by domi nance of Th1-lymphocytes in immune responses and development of acute GVHD with pronounced tissue destruction and mass death of recipient animals. If DBA/2 mice are used as donors, a different type of immune conflict develops in recipient mice: chronic GVHD with predominance of Th2dependent reactions, intense polyclonal activation of B-lymphocytes, overproduction of antibodies and development of immunocomplex glomerulonephritis in some animals. It is possible to shift the balance of T-helper cells in either direction by using various immunomodulatory agents. It makes this model a convenient and sensitive test-system for identifying
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