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Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution

Understanding the evolution of interleukins and interleukin receptors is essential to control the function of CD4+ T cells in various pathologies. Numerous aspects of CD4+ T cells’ presence are controlled by interleukins including differentiation, proliferation, and plasticity. CD4+ T cells have eme...

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Autores principales: Kubick, Norwin, Klimovich, Pavel, Flournoy, Patrick Henckell, Bieńkowska, Irmina, Łazarczyk, Marzena, Sacharczuk, Mariusz, Bhaumik, Suniti, Mickael, Michel-Edwar, Basu, Rajatava
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226699/
https://www.ncbi.nlm.nih.gov/pubmed/34073576
http://dx.doi.org/10.3390/genes12060813
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author Kubick, Norwin
Klimovich, Pavel
Flournoy, Patrick Henckell
Bieńkowska, Irmina
Łazarczyk, Marzena
Sacharczuk, Mariusz
Bhaumik, Suniti
Mickael, Michel-Edwar
Basu, Rajatava
author_facet Kubick, Norwin
Klimovich, Pavel
Flournoy, Patrick Henckell
Bieńkowska, Irmina
Łazarczyk, Marzena
Sacharczuk, Mariusz
Bhaumik, Suniti
Mickael, Michel-Edwar
Basu, Rajatava
author_sort Kubick, Norwin
collection PubMed
description Understanding the evolution of interleukins and interleukin receptors is essential to control the function of CD4+ T cells in various pathologies. Numerous aspects of CD4+ T cells’ presence are controlled by interleukins including differentiation, proliferation, and plasticity. CD4+ T cells have emerged during the divergence of jawed vertebrates. However, little is known about the evolution of interleukins and their origin. We traced the evolution of interleukins and their receptors from Placozoa to primates. We performed phylogenetic analysis, ancestral reconstruction, HH search, and positive selection analysis. Our results indicated that various interleukins’ emergence predated CD4+ T cells divergence. IL14 was the most ancient interleukin with homologs in fungi. Invertebrates also expressed various interleukins such as IL41 and IL16. Several interleukin receptors also appeared before CD4+ T cells divergence. Interestingly IL17RA and IL17RD, which are known to play a fundamental role in Th17 CD4+ T cells first appeared in mollusks. Furthermore, our investigations showed that there is not any single gene family that could be the parent group of interleukins. We postulate that several groups have diverged from older existing cytokines such as IL4 from TGFβ, IL10 from IFN, and IL28 from BCAM. Interleukin receptors were less divergent than interleukins. We found that IL1R, IL7R might have diverged from a common invertebrate protein that contained TIR domains, conversely, IL2R, IL4R and IL6R might have emerged from a common invertebrate ancestor that possessed a fibronectin domain. IL8R seems to be a GPCR that belongs to the rhodopsin-like family and it has diverged from the Somatostatin group. Interestingly, several interleukins that are known to perform a critical function for CD4+ T cells such as IL6, IL17, and IL1B have gained new functions and evolved under positive selection. Overall evolution of interleukin receptors was not under significant positive selection. Interestingly, eight interleukin families appeared in lampreys, however, only two of them (IL17B, IL17E) evolved under positive selection. This observation indicates that although lampreys have a unique adaptive immune system that lacks CD4+ T cells, they could be utilizing interleukins in homologous mode to that of the vertebrates’ immune system. Overall our study highlights the evolutionary heterogeneity within the interleukins and their receptor superfamilies and thus does not support the theory that interleukins evolved solely in jawed vertebrates to support T cell function. Conversely, some of the members are likely to play conserved functions in the innate immune system.
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spelling pubmed-82266992021-06-26 Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution Kubick, Norwin Klimovich, Pavel Flournoy, Patrick Henckell Bieńkowska, Irmina Łazarczyk, Marzena Sacharczuk, Mariusz Bhaumik, Suniti Mickael, Michel-Edwar Basu, Rajatava Genes (Basel) Article Understanding the evolution of interleukins and interleukin receptors is essential to control the function of CD4+ T cells in various pathologies. Numerous aspects of CD4+ T cells’ presence are controlled by interleukins including differentiation, proliferation, and plasticity. CD4+ T cells have emerged during the divergence of jawed vertebrates. However, little is known about the evolution of interleukins and their origin. We traced the evolution of interleukins and their receptors from Placozoa to primates. We performed phylogenetic analysis, ancestral reconstruction, HH search, and positive selection analysis. Our results indicated that various interleukins’ emergence predated CD4+ T cells divergence. IL14 was the most ancient interleukin with homologs in fungi. Invertebrates also expressed various interleukins such as IL41 and IL16. Several interleukin receptors also appeared before CD4+ T cells divergence. Interestingly IL17RA and IL17RD, which are known to play a fundamental role in Th17 CD4+ T cells first appeared in mollusks. Furthermore, our investigations showed that there is not any single gene family that could be the parent group of interleukins. We postulate that several groups have diverged from older existing cytokines such as IL4 from TGFβ, IL10 from IFN, and IL28 from BCAM. Interleukin receptors were less divergent than interleukins. We found that IL1R, IL7R might have diverged from a common invertebrate protein that contained TIR domains, conversely, IL2R, IL4R and IL6R might have emerged from a common invertebrate ancestor that possessed a fibronectin domain. IL8R seems to be a GPCR that belongs to the rhodopsin-like family and it has diverged from the Somatostatin group. Interestingly, several interleukins that are known to perform a critical function for CD4+ T cells such as IL6, IL17, and IL1B have gained new functions and evolved under positive selection. Overall evolution of interleukin receptors was not under significant positive selection. Interestingly, eight interleukin families appeared in lampreys, however, only two of them (IL17B, IL17E) evolved under positive selection. This observation indicates that although lampreys have a unique adaptive immune system that lacks CD4+ T cells, they could be utilizing interleukins in homologous mode to that of the vertebrates’ immune system. Overall our study highlights the evolutionary heterogeneity within the interleukins and their receptor superfamilies and thus does not support the theory that interleukins evolved solely in jawed vertebrates to support T cell function. Conversely, some of the members are likely to play conserved functions in the innate immune system. MDPI 2021-05-26 /pmc/articles/PMC8226699/ /pubmed/34073576 http://dx.doi.org/10.3390/genes12060813 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kubick, Norwin
Klimovich, Pavel
Flournoy, Patrick Henckell
Bieńkowska, Irmina
Łazarczyk, Marzena
Sacharczuk, Mariusz
Bhaumik, Suniti
Mickael, Michel-Edwar
Basu, Rajatava
Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution
title Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution
title_full Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution
title_fullStr Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution
title_full_unstemmed Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution
title_short Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution
title_sort interleukins and interleukin receptors evolutionary history and origin in relation to cd4+ t cell evolution
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226699/
https://www.ncbi.nlm.nih.gov/pubmed/34073576
http://dx.doi.org/10.3390/genes12060813
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