Retinal Self-Antigen Induces a Predominantly Th1 Effector Response in Axl and Mertk Double-Knockout Mice
| Autor: | Zhenwen Chen, Lixia Han, Wanwei Dong, Qingjun Lu, Fei Ye, Qiutang Li, Henry J. Kaplan, Hui Shao, Qingxian Lu |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cellular differentiation
Immunology Autoimmunity Enzyme-Linked Immunosorbent Assay Stimulation Biology Lymphocyte Activation medicine.disease_cause Autoantigens Retina Article Flow cytometry Mice Antigen Proto-Oncogene Proteins medicine Animals Immunology and Allergy Receptor Mice Knockout c-Mer Tyrosine Kinase medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction Effector Macrophages Receptor Protein-Tyrosine Kinases Cell Differentiation Dendritic Cells Th1 Cells MERTK Flow Cytometry Axl Receptor Tyrosine Kinase Molecular biology Cell biology Mice Inbred C57BL Cytokines |
| Zdroj: | The Journal of Immunology. 187:4178-4186 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1101201 |
| Popis: | The TAM family of receptors (Tyro3, Axl, and Mertk) plays an important role in the negative regulation of response of dendritic cells (DCs) and macrophages to pathogenic stimuli, and mice lacking this receptor family develop spontaneous lupus-like systemic autoimmunity against a variety of tissues, including retina. To study the molecular mechanism underlying the TAM regulation of APC functions and subsequent effects on the induction of an autoimmune response against the eye, we examined CD4 T cell differentiation following retinal self-antigen immunization. CD4 T cells prepared from naive or interphotoreceptor retinoid-binding protein (IRBP)1-20–immunized Axl and Mertk double-knockout (dko) mice reacted to activation using anti-CD3 and anti-CD28 Abs or to bolster by self-antigen in vitro with a predominantly Th1 effector response, as characterized by increased IFN-γ production and higher frequency of IFN-γ–positive CD4 T cells. The Th17 effector response to IRBP immunization was similar in dko mice to that in wild-type controls, as shown by ELISA measurement of IL-17A in the culture medium and flow cytometric analysis of IL-17A–secreting CD4 T cells. Interestingly, APCs or DCs isolated from IRBP-immunized dko mice exhibited a greater ability to drive the Th1 response. The production of two driving cytokines for Th1 differentiation, IL-12 and IL-18, was dramatically increased in dko DCs and macrophages, and LPS stimulation bolstered their production. The preferential development into the Th1 subset in dko mice suggests that the cytokine milieu produced by the mutant mice in vivo or by mutant APCs in vitro selectively creates a differentiation environment favoring the Th1 effector response. |
| Databáze: | OpenAIRE |
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