mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-FAR-2235mimmun-2235Research ArticleМАТЕРИАЛЫ ФОРУМА "ДНИ ИММУНОЛОГИИ В СПБ" 2021РЕЦЕПТОР ЖИРНЫХ КИСЛОТ GPR84 И Th1/Th2-БАЛАНС В ЭКСПЕРИМЕНТАЛЬНОЙ СИСТЕМЕ IN VIVOFATTY ACID RECEPTOR GPR84 AND Th1/Th2 BALANCE IN THE EXPERIMENTAL SYSTEM IN VIVOДемченкоЕ. Н.DemchenkoE. N.

 к.х.н., научный сотрудник лаборатории экспериментальной иммунотерапии,

630099, г. Новосибирск, ул. Ядринцевская, 14

PhD (Chemistry), Research Associate, Laboratory of Experimental Immunotherapy,

630099, Novosibirsk, Yadrintsevskaya str., 14

elena.demchenko@gmail.comhttps://orcid.org/0000-0002-2014-3397ГавриловаЕ. Д.GavrilovaE. D.

 к.б.н., заведующий лабораторией экспериментальной иммунотерапии,

630099, г. Новосибирск, ул. Ядринцевская, 14

PhD (Biology), Head, Laboratory of Experimental Immunotherapy,

630099, Novosibirsk, Yadrintsevskaya str., 14

edav.gavr@mail.ruhttps://orcid.org/0000-0002-6443-6917ГойманЕ. В.GoimanE. V.

к.м.н., научный сотрудник лаборатории экспериментальной иммунотерапии,

630099, г. Новосибирск, ул. Ядринцевская, 14

PhD (Medicine), Research Associate, Laboratory of Experimental Immunotherapy,

630099, Novosibirsk, Yadrintsevskaya str., 14

l.goiman@mail.ruВольскийН. Н.VolckiyN. N.

к.м.н., ведущий научный сотрудник лаборатории экспериментальной иммунотерапии,

630099, г. Новосибирск, ул. Ядринцевская, 14

PhD (Medicine), Leading Research Associate, Laboratory of Experimental Immunotherapy, 

630099, Novosibirsk, Yadrintsevskaya str., 14

dtheory@yandex.ruФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии»Research Institute of Fundamental and Clinical Immunology202108102021234659664Copyright © Демченко Е.Н., Гаврилова Е.Д., Гойман Е.В., Вольский Н.Н., 20212021Демченко Е.Н., Гаврилова Е.Д., Гойман Е.В., Вольский Н.Н.Demchenko E.N., Gavrilova E.D., Goiman E.V., Volckiy N.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2235

В ходе многочисленных исследований, в том числе в нашей лаборатории, было обнаружено, что баланс Th1/Th2 играет важную роль в регуляции реакций, определяющих исход иммунопатологических процессов как в моделях хронической РТПХ, так и в моделях острой РТПХ. Однако до сих пор открыт вопрос: от активности какого именно элемента регуляторного процесса в момент индукции РТПХ (например рецептора или фермента) зависит соотношение этого баланса. Сделано предположение, что степень активации рецептора GPR84 в момент индукции РТПХ может существенно влиять на Th1/Th2-баланс в организме и благодаря этому определяет направление развития и интенсивность патологического процесса. Целью настоящей работы являлось изучить влияние лигандов рецептора среднецепочечных жирных кислот GPR84 на баланс Th1/Th2 в экспериментальной модели in vivo.

В экспериментах были использованы самки мышей линий DBA/2 и гибридов (C57Bl/6 × DBA/2)F. В качестве исследуемых лигандов GPR84 использовали каприновую и лауриновую кислоты, а также синтетический лиганд 6-OAU. Хроническую РТПХ в полуаллогенной системе индуцировали вводя спленоциты мышей DBA/2 мышам-гибридам B6D2F1: по 60-70 × 106 клеток в/в двукратно с интервалом в 6 дней. Первое введение лигандов GPR84 производили через час после переноса донорских клеток и затем раз в сутки в течение двух недель. Эффект воздействия исследуемых препаратов на течение хронической РТПХ оценивали через три месяца после начала экспериментa.

Было показано, что введение животным лигандов к GPR84 в ходе индукции хронической РТПХ влияет на активность рецептора и на Th1/Th2-соотношение в организме. Введение синтетического лиганда 6-OAU увеличило количество животных, у которых иммунопатологический процесс развивался по Th1-зависимому варианту, почти в полтора раза по сравнению с группой без введения лиганда, что соответствовало литературным данным, полученным в системе in vitro. Эффект смеси каприновой и лауриновой кислот, видимо, опосредуется каким-то иным механизмом, отличным от активации GPR84. Следовательно, для осуществления перспективной возможности корректировать иммунные реакции путем включения в диету определенных жирных кислот требуются дальнейшие исследования. 

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.  

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The authors declare that there are no conflicts of interest present.