title: Evolution of IL4 and pathogen antagonism.
abstract: Interleukin-4 (IL4) is a pleiotropic cytokine involved in host protection from gastrointestinal nematodes. Here, we review the structure, function, and evolutionary history of IL4. Cumulative evidence indicates that over 100 million years of eutherian mammalian evolution, IL4 has experienced multiple episodes of positive selection. We argue that IL4 may have evolved in conflict with pathogen-derived antagonists, and therefore diversified to escape antagonism while being constrained to maintain binding to its cellular receptors. Selective pressure driving IL4 diversification may have arisen from ancient episodes of conflict with parasitic worm-derived IL4 antagonists. Descendants of such antagonists may still equip the armamentarium of contemporary gastrointestinal nematodes.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Meenu R
authors.initials: MR
authors.lastname: Pillai
authors.forename: Mark
authors.initials: M
authors.lastname: Bix
mesh_terms: D000818:Animals; D005075:Biological Evolution; D019143:Evolution, Molecular; D041981:Gastrointestinal Tract / Q000276:immunology / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D017578:Immunoglobulin Class Switching; D015847:Interleukin-4 / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D053662:Interleukin-4 Receptor alpha Subunit / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D009348:Nematoda / Q000276:immunology* / Q000378:metabolism; D009349:Nematode Infections / Q000276:immunology*; D011485:Protein Binding; D012641:Selection, Genetic
chemical_list: D053662:Interleukin-4 Receptor alpha Subunit; D015847:Interleukin-4