Surfactant protein-A inhibits thymic stromal lymphopoietin-mediated T follicular helper cell differentiation and IgE production in asthma
| Autor: | Li Su, Siwei He, Shuqin Xu, Minghui Xue, Xiaomeng Nie, Lin Lin, Cunpeng Ji, Beiying Wu, Gang Cai |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Thymic stromal lymphopoietin T Follicular Helper Cells Immunology Immunoglobulin E Lymphocyte Activation Allergic inflammation Mice Thymic Stromal Lymphopoietin Follicular phase Immunology and Allergy Animals Humans Aged Mice Knockout T follicular helper cell differentiation biology Pulmonary Surfactant-Associated Protein A Chemistry Cell Differentiation Dendritic Cells Middle Aged Asthma Surfactant protein A Mice Inbred C57BL Ovalbumin biology.protein Cytokines Female Protein A |
| Zdroj: | Clinical immunology (Orlando, Fla.). 231 |
| ISSN: | 1521-7035 |
| Popis: | Lung surfactant protein A (SP-A) is critical for immunomodulation. Thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) drive T follicular helper (Tfh) cells differentiation in allergic asthma. We employed wild-type (WT) and SP-A-/- mice injected with TSLP and ovalbumin (OVA)-activated DCs and challenged with OVA. Compared with WT mice, we showed that allergic inflammation was dramatically increased in SP-A-/- mice. In parallel, both IL-4-producing CD45RA-CXCR5+PD-1+CD4+ cells (Tfh2) and IgE were markedly increased in SP-A-/- mice. Further study showed that SP-A prohibited TSLP activated-DCs from expressing OX40L. When we blocked OX40L-OX40 and IL-4R signaling, the differentiation of Tfh2 and IgE responses in SP-A-/- mice was significantly inhibited. In severe asthma patients, SP-A is dysfunctional in modulating the TSLP-DCs-mediated differentiation of Tfh cells. This study suggests that SP-A acts as a modulator of Tfh differentiation and IgE generation in asthma. |
| Databáze: | OpenAIRE |
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