Implication of the Transmembrane Domain in the Interleukin 10 Receptor Platform Oligomerisation

Thomas Kuntzel; Caroline Spenlé; Lucas D Pham-Van; Dafni Birmpili; Aurélien Riou; Aurore Loeuillet; Imane Charmarke-Askar; Dominique Bagnard

doi:10.3390/cells12101361

Implication of the Transmembrane Domain in the Interleukin 10 Receptor Platform Oligomerisation

Cells. 2023 May 10;12(10):1361. doi: 10.3390/cells12101361.

Authors

Thomas Kuntzel¹, Caroline Spenlé¹, Lucas D Pham-Van¹, Dafni Birmpili¹, Aurélien Riou¹, Aurore Loeuillet¹, Imane Charmarke-Askar¹, Dominique Bagnard^{1

2}

Affiliations

¹ UMR7242 Biotechnology and Cell Signalling, Centre National de la Recherche Scientifique, Strasbourg Drug Discovery and Development Institute (IMS), University of Strasbourg, 67400 Illkirch-Graffenstaden, France.
² Ecole Supérieure de Biotechnologie de Strasbourg, 67400 Illkirch-Graffenstaden, France.

Abstract

Interleukin 10 (IL-10) exerts anti-inflammatory and immune regulatory roles through its fixation to the IL-10 receptor (IL-10R). The two subunits (IL-10Rα and IL-10Rβ) organise themselves to form a hetero-tetramer to induce the activation of the transcription factor STAT3. We analysed the activation patterns of the IL-10R, especially the contribution of the transmembrane (TM) domain of the IL-10Rα and IL-10Rβ subunits, as evidence accumulates that this short domain has tremendous implications in receptor oligomerisation and activation. We also addressed whether targeting the TM domain of IL-10R with peptides mimicking the TM sequences of the subunits translates into biological consequences. The results illustrate the involvement of the TM domains from both subunits in receptor activation and feature a distinctive amino acid crucial for the interaction. The TM peptide targeting approach also appears to be suitable for modulating the activation of the receptor through its action on the dimerization capabilities of the TM domains and thereby constitutes a potential new strategy for the modulation of the inflammation in pathologic contexts.

Keywords: interleukin 10; macrophage; peptide; transmembrane domain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids
Gene Expression Regulation*
Receptors, Interleukin-10
Signal Transduction
Transcription Factors*

Substances

Receptors, Interleukin-10
Transcription Factors
Amino Acids

Grants and funding

This work of the Drug Discovery and Development Institute (IMS) is part of the Interdisciplinary Thematic Institute (ITI) 2021–2028 program of the University of Strasbourg, CNRS and Inserm, was supported by IdEx Unistra (ANR-10-IDEX-0002) and by the SFRI-STRAT’US project (ANR-20-SFRI-0012) under the framework of the French Investments for the Future Program.