title: Thymic stromal lymphopoietin amplifies the differentiation of alternatively activated macrophages.
abstract: The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) has been associated with the promotion of type 2 inflammation and the induction of allergic disease. In humans TSLP is elevated in the lungs of asthma patients and in the lesional skin of individuals with atopic dermatitis, whereas mice lacking TSLP responses are refractory to models of Th2-driven allergic disease. Although several cell types, including dendritic cells, basophils, and CD4 T cells, have been shown to respond to TSLP, its role in macrophage differentiation has not been studied. Type 2 cytokines (i.e., IL-4 and IL-13) can drive the differentiation of macrophages into alternatively activated macrophages (aaMs, also referred to as M2 macrophages). This population of macrophages is associated with allergic inflammation. We therefore reasoned that TSLP/TSLPR signaling may be involved in the differentiation and activation of aaMs during allergic airway inflammation. In this study, we report that TSLP changes the quiescent phenotype of pulmonary macrophages toward an aaM phenotype during TSLP-induced airway inflammation. This differentiation of airway macrophages was IL-13-, but not IL-4-, dependent. Taken together, we demonstrate in this study that TSLP/TSLPR plays a significant role in the amplification of aaMΦ polarization and chemokine production, thereby contributing to allergic inflammation.
authors.affiliation: Immunology Program, Benaroya Research Institute, Seattle, WA 98101, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Han
authors.forename: Mark B
authors.initials: MB
authors.lastname: Headley
authors.forename: Whitney
authors.initials: W
authors.lastname: Xu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Comeau
authors.forename: Baohua
authors.initials: B
authors.lastname: Zhou
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000187:drug effects; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018793:Interleukin-13 / Q000172:deficiency / Q000502:physiology; D015847:Interleukin-4 / Q000172:deficiency / Q000502:physiology; D008168:Lung / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000633:toxicity; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D050800:STAT6 Transcription Factor / Q000172:deficiency / Q000502:physiology; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D018925:Chemokines; D016207:Cytokines; D007136:Immunoglobulins; D018793:Interleukin-13; D018121:Receptors, Cytokine; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C410591:Tslpr protein, mouse; D015847:Interleukin-4; D010047:Ovalbumin; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse