PT  - JOURNAL ARTICLE
AU  - Enten, Garrett A
AU  - Gao, Xianlong
AU  - McGee, Michelle Y
AU  - Weche, McWayne
AU  - Majetschak, Matthias
TI  - Chemokine receptor hetero-oligomers regulate monocyte chemotaxis
AID  - 10.26508/lsa.202402657
DP  - 2024 Aug 01
TA  - Life Science Alliance
PG  - e202402657
VI  - 7
IP  - 8
4099  - http://www.life-science-alliance.org/content/7/8/e202402657.short
4100  - http://www.life-science-alliance.org/content/7/8/e202402657.full
SO  - Life Sci. Alliance2024 Aug 01; 7
AB  - It is known that stress influences immune cell function. The underlying molecular mechanisms are unclear. We recently reported that many chemokine receptors (CRs) heteromerize with α1-adrenoceptors (α1-ARs) through which CRs are regulated. Here, we show that arginine vasopressin receptor 1A (AVPR1A) heteromerizes with all human CRs, except chemokine (C-X-C motif) receptor (CXCR)1, in recombinant systems and that such heteromers are detectable in THP-1 cells and human monocytes. We demonstrate that ligand-free AVPR1A differentially regulates the efficacy of CR partners to mediate chemotaxis and that AVPR1A ligands disrupt AVPR1A:CR heteromers, which enhances chemokine (C-C motif) receptor (CCR)1-mediated chemotaxis and inhibits CCR2-, CCR8-, and CXCR4-mediated chemotaxis. Using bioluminescence resonance energy transfer to monitor G protein activation and CRISPR/Cas9 gene-edited THP-1 cells lacking AVPR1A or α1B-AR, we show that CRs that share the propensity to heteromerize with α1B/D-ARs and AVPR1A exist and function within interdependent hetero-oligomeric complexes through which the efficacy of CRs to mediate chemotaxis is controlled. Our findings suggest that hetero-oligomers composed of CRs, α1B/D-ARs, and AVPR1A may enable stress hormones to regulate immune cell trafficking.All datasets are included in the study.Ethics statementThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the University of South Florida (Pro00037030/Date 07/13/2023).Consent to participateInformed consent was obtained from all individual participants included in the study.Consent for publicationConsent to publish has been received from all participants.