PreprintArticleVersion 1This version is not peer-reviewed
Chemokinergic and Dopaminergic Signalling Collaborates through the Heteromer Formed by CCR9 and Dopamine Receptor D5 Increasing the Migratory Speed of Effector CD4+ T-Cells to Infiltrate the Colonic Mucosa
Version 1
: Received: 13 August 2024 / Approved: 14 August 2024 / Online: 14 August 2024 (16:40:26 CEST)
How to cite:
Campos, J.; Osorio-Barrios, F.; Villanelo, F.; Gutierrez-Maldonado, S. E.; Vargas, P.; Perez-Acle, T.; Pacheco, R. Chemokinergic and Dopaminergic Signalling Collaborates through the Heteromer Formed by CCR9 and Dopamine Receptor D5 Increasing the Migratory Speed of Effector CD4+ T-Cells to Infiltrate the Colonic Mucosa. Preprints2024, 2024081063. https://doi.org/10.20944/preprints202408.1063.v1
Campos, J.; Osorio-Barrios, F.; Villanelo, F.; Gutierrez-Maldonado, S. E.; Vargas, P.; Perez-Acle, T.; Pacheco, R. Chemokinergic and Dopaminergic Signalling Collaborates through the Heteromer Formed by CCR9 and Dopamine Receptor D5 Increasing the Migratory Speed of Effector CD4+ T-Cells to Infiltrate the Colonic Mucosa. Preprints 2024, 2024081063. https://doi.org/10.20944/preprints202408.1063.v1
Campos, J.; Osorio-Barrios, F.; Villanelo, F.; Gutierrez-Maldonado, S. E.; Vargas, P.; Perez-Acle, T.; Pacheco, R. Chemokinergic and Dopaminergic Signalling Collaborates through the Heteromer Formed by CCR9 and Dopamine Receptor D5 Increasing the Migratory Speed of Effector CD4+ T-Cells to Infiltrate the Colonic Mucosa. Preprints2024, 2024081063. https://doi.org/10.20944/preprints202408.1063.v1
APA Style
Campos, J., Osorio-Barrios, F., Villanelo, F., Gutierrez-Maldonado, S. E., Vargas, P., Perez-Acle, T., & Pacheco, R. (2024). Chemokinergic and Dopaminergic Signalling Collaborates through the Heteromer Formed by CCR9 and Dopamine Receptor D5 Increasing the Migratory Speed of Effector CD4+ T-Cells to Infiltrate the Colonic Mucosa. Preprints. https://doi.org/10.20944/preprints202408.1063.v1
Chicago/Turabian Style
Campos, J., Tomas Perez-Acle and Rodrigo Pacheco. 2024 "Chemokinergic and Dopaminergic Signalling Collaborates through the Heteromer Formed by CCR9 and Dopamine Receptor D5 Increasing the Migratory Speed of Effector CD4+ T-Cells to Infiltrate the Colonic Mucosa" Preprints. https://doi.org/10.20944/preprints202408.1063.v1
Abstract
Inflammatory bowel diseases (IBD) involve chronic inflammation of the gastrointestinal tract, where effector CD4+ T-cells play a central role. Thereby, the recruitment of T-cells into the colonic mucosa represents a key process in IBD. We recently found that CCR9 and DRD5 might form a heteromeric complex on the T-cell surface. The increase of CCL25 production and the reduction in dopamine levels associated with colonic inflammation represent a dual signal stimulating the CCR9:DRD5 heteromer, which promotes the recruitment of CD4+ T-cells into the colonic lamina propria. Here, we aimed to analysing the molecular requirements involved in the heteromer assembly as well as to determining the underlying cellular mechanisms involved in the colonic tropism given by the stimulation of the CCR9:DRD5 complex. The results show that dual stimulation of the CCR9:DRD5 heteromer potentiates the phosphorylation of the myosin light chain 2 (MLC2) and the migration speed in confined microchannels. Accordingly, disrupting the CCR9:DRD5 assembly induced a sharp reduction in the pMLC2 in vitro, decreased the migratory speed in confined microchannels and dampened the recruitment of CD4+ T-cells into the inflamed colonic mucosa. Furthermore, in silico analysis confirmed that the interface of interaction of CCR9:DRD5 is formed by the transmembrane segments 5 and 6 from each protomer. Our findings demonstrated that the CCR9:DRD5 heteromeric complex plays a fundamental role in the migration of CD4+ T-cells into the colonic mucosa upon inflammation. Thereby, disassembling the formation of the CCR9:DRD5 represents an important therapeutic opportunity to treat IBD.
Keywords
Dopamine; chemokines; T cell migration
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
