The transcriptional repressor BLIMP1 curbs host defenses by suppressing expression of the chemokine CCL8

摘要: The transcriptional repressor B lymphocyte-induced maturation protein 1 (BLIMP1) is a master regulator of and T cell differentiation. To examine the role BLIMP1 in innate immunity, we used conditional knockout (CKO) Blimp1 myeloid cells found that CKO mice were protected from lethal infection induced by Listeria monocytogenes. Transcriptome analysis macrophages identified murine chemokine (C-C motif) ligand 8, CCL8, as direct target Blimp1-mediated repression these cells. BLIMP1-deficient expressed elevated levels Ccl8, consequently had higher circulating resulting increased neutrophils peripheral blood, promoting more aggressive antibacterial response. Mice lacking Ccl8 gene susceptible to L. monocytogenes than wild-type mice. Although CCL8 failed recruit directly, it was chemotactic for γ/δ cells, CCL8-responsive enriched IL-17F. Finally, CCL8-mediated enhanced clearance dependent on Collectively, data reveal an important modulating host defenses suppressing expression CCL8.