title: IL-13Rα1 is a surface marker for M2 macrophages influencing their differentiation and function.
abstract: In this study, we examined the role IL-13 receptor alpha 1 (IL-13Rα1) plays in macrophage differentiation and function. The findings indicate that IL-13Rα1 is expressed on the M2 but not on the M1 subset of macrophages and specifically heterodimerizes with the IL-4Rα chain to form a type II receptor, which controls the differentiation and function of these cells. Indeed, BM cells from IL-13Rα1(+/+) and IL-13Rα1(-/-) mice yield equivalent numbers of macrophages when cultured under M2 polarizing conditions. However, IL-13Rα1(-/-) BM cells yield a much higher number of macrophages than IL-13Rα1(+/+) BM cells when the differentiation is carried out under M1-polarizing conditions. Further analyses indicated that macrophages that express IL-13Rα1 also display surface markers associated with an M2 phenotype. In addition, the IL-13Rα1(+) macrophages were highly efficient in phagocytizing zymosan bioparticles both in vitro and in vivo, and supported differentiation of naïve T cells to a Th2 phenotype. Finally, when stimulated by IL-13, a cytokine that uses the heteroreceptor, the cells were able to phosphorylate STAT6 efficiently. These previously unrecognized findings indicate that IL-13Rα1 serves as a marker for M2 macrophages and the resulting heteroreceptor influences both their differentiation and function.
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Missouri School of Medicine, Columbia, MO, USA.
authors.forename: Mermagya
authors.initials: M
authors.lastname: Dhakal
authors.forename: John C
authors.initials: JC
authors.lastname: Hardaway
authors.forename: Fatma Betul
authors.initials: FB
authors.lastname: Guloglu
authors.forename: Mindy M
authors.initials: MM
authors.lastname: Miller
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hoeman
authors.forename: Adam A
authors.initials: AA
authors.lastname: Zaghouani
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wan
authors.forename: Linda M
authors.initials: LM
authors.lastname: Rowland
authors.forename: Jason A
authors.initials: JA
authors.lastname: Cascio
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sherman
authors.forename: Habib
authors.initials: H
authors.lastname: Zaghouani
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D016130:Immunophenotyping; D018793:Interleukin-13 / Q000494:pharmacology; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D019655:Quantitative Trait, Heritable; D050800:STAT6 Transcription Factor / Q000378:metabolism
chemical_list: D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D050800:STAT6 Transcription Factor
keywords: Antigen presentation; Differentiation; IL-13 Rα1; Macrophages; Phagocytosis