Evolutionary divergence and functions of the human interleukin (IL) gene family

Brocker, Chad; Thompson, David; Matsumoto, Akiko; Nebert, Daniel W; Vasiliou, Vasilis

doi:10.1186/1479-7364-5-1-30

Cited by 368Cytokine Signaling Pathways and InteractionsImmune Response and InflammationChemokine receptors and signaling

Evolutionary divergence and functions of the human interleukin (IL) gene family

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Brocker, Chad, Thompson, David, Matsumoto, Akiko, Nebert, Daniel W, Vasiliou, Vasilis·2010·Human Genomics

DOI 10.1186/1479-7364-5-1-30PMC PMC3390169

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Abstract

Cytokines play a very important role in nearly all aspects of inflammation and immunity. The term 'interleukin' (IL) has been used to describe a group of cytokines with complex immunomodulatory functions - including cell proliferation, maturation, migration and adhesion. These cytokines also play an important role in immune cell differentiation and activation. Determining the exact function of a particular cytokine is complicated by the influence of the producing cell type, the responding cell type and the phase of the immune response. ILs can also have pro- and anti-inflammatory effects, further complicating their characterisation. These molecules are under constant pressure to evolve due to continual competition between the host's immune system and infecting organisms; as such, ILs have undergone significant evolution. This has resulted in little amino acid conservation between orthologous proteins, which further complicates the gene family organisation. Within the literature there are a number of overlapping nomenclature and classification systems derived from biological function, receptor-binding properties and originating cell type. Determining evolutionary relationships between ILs therefore can be confusing. More recently, crystallographic data and the identification of common structural motifs have led to a more accurate classification system. To date, the known ILs can be divided into four major groups based on distinguishing structural features. These groups include the genes encoding the IL1-like cytokines, the class I helical cytokines (IL4-like, γ-chain and IL6/12-like), the class II helical cytokines (IL10-like and IL28-like) and the IL17-like cytokines. In addition, there are a number of ILs that do not fit into any of the above groups, due either to their unique structural features or lack of structural information. This suggests that the gene family organisation may be subject to further change in the near future.

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Authors: Brocker, C., Thompson, D., Matsumoto, A., Nebert, D. W., & Vasiliou, V.
Affiliations: University of Colorado Denver (US)
University of Cincinnati Medical Center (US)
Corresponding author: Nebert, Daniel W
ORCID: Brocker, Chad
Matsumoto, Akiko
Vasiliou, Vasilis
Venue: Human Genomics
Publisher: Springer Science and Business Media LLC
Published: 2010
Volume: 5
Issue: 1
Pages: 30
ISSN: 1473-9542 (ISSN-L)
1479-7364
DOI: 10.1186/1479-7364-5-1-30
PMC: PMC3390169
OpenAlex: W2127751957
Cited by: 368
References: 185
Citations by year: 2026: 18 · 2025: 24 · 2024: 21 · 2023: 36 · 2022: 42 · 2021: 46 · 2020: 43 · 2019: 18 · 2018: 24 · 2017: 23 · 2016: 22 · 2015: 24 · 2014: 16 · 2013: 9 · 2012: 2
FWCI: 1.74
Type: journal article
Language: en
Open access: gold
doi.org
Locations: Human Genomics (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health
National Institute on Alcohol Abuse and Alcoholism (R21AA017754, F31AA018248)
National Eye Institute (R01EY017963, R01EY17963)
National Institute of Environmental Health Sciences (P30ES006096, P30 ES-06096)
Topics: Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Keywords: cytokines, evolutionary divergence, cytokine structure, orthologous proteins, amino acid conservation, immune response, inflammation
MeSH terms: Multigene Family, Humans, Interleukins, Terminology as Topic, Phylogeny, Protein Conformation, Cluster Analysis, Cytokines, Evolution, Molecular

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Evolutionary divergence and functions of the human interleukin (IL) gene family

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