Extracellular matrix protein 1 promotes follicular helper T cell differentiation and antibody production.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30087185.
- Also identified by DOI 10.1073/pnas.1801196115 and PMC identifier 6112729.
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Abstract
T-follicular helper (T<sub>FH</sub>) cells are a subset of CD4<sup>+</sup> helper T cells that help germinal center (GC) B-cell differentiation and high-affinity antibody production during germinal center reactions. Whether important extracellular molecules control T<sub>FH</sub> differentiation is not fully understood. Here, we demonstrate that a secreted protein extracellular matrix protein 1 (ECM1) is critical for T<sub>FH</sub> differentiation and antibody response. A lack of ECM1 inhibited T<sub>FH</sub> cell development and impaired GC B-cell reactions and antigen-specific antibody production in an antigen-immunized mouse model. ECM1 was induced by IL-6 and IL-21 in T<sub>FH</sub> cells, promoting T<sub>FH</sub> differentiation by down-regulating the level of STAT5 phosphorylation and up-regulating Bcl6 expression. Furthermore, injection of recombinant ECM1 protein into mice infected with PR8 influenza virus promoted protective immune responses effectively, by enhancing T<sub>FH</sub> differentiation and neutralizing antibody production. Collectively, our data identify ECM1 as a soluble protein to promote T<sub>FH</sub> cell differentiation and antibody production.
Medical subject headings
- Antibody Formation
- B-Lymphocytes
- Cell Differentiation
- Extracellular Matrix Proteins
- T-Lymphocytes, Helper-Inducer