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The Role of SDF‐1/CXCR4 axis in Th17 migration to bone marrow
Author(s) -
Zheng Mingquan,
McKinly Laura,
Kolls Jay
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1069.3
Subject(s) - bone marrow , chemokine , immunology , haematopoiesis , proinflammatory cytokine , stromal cell , cxcr4 , cytokine , cxcr3 , lung , cxcl16 , chemistry , medicine , chemokine receptor , biology , inflammation , stem cell , cancer research , microbiology and biotechnology
The chemokine receptor CXCR4 and its unique ligand, stromal‐derived factor 1 (SDF‐1, also called CXCL12), play critical roles in the recruitment and retention of hematopoietic cells within bone marrow and in their mobilization into the circulation. Its interactions directboth the recruitment of different infiltrating cell types tothe lung and the production of inflammatory mediators that intensifypulmonary damage. During lung infection, the T helper cells (Th)17 produce and release the proinflammatory cytokine IL‐17, IL‐17F and IL‐22 which controls CXC chemokine, G‐CSF and antimicrobial protein production in the lung. We hypothesized that Th17 cells are also recruited to sites of granulopoiesis and that CXCR4 signaling is required for the migration of IL‐17 producing T‐cells to these sites. Widetype(WT) mice were treated with anti‐CXCR4, anti‐SDF‐1, or control Ab followed by challenge with K. pneumoniae (KP). Ouctome measures included survival, complete blood counts in peripheral blood, serum and lung cytokines and chemokines, and Th17 precurosr frequncey by Elispot. CXC4 is express on approximately 5% of in vitro polarized Th17 cells grown in Th17 condition media. WT mice showed an increase in Th17 cells by Elsipot in both the lung and bone marrow 18 hours after Kp infection. Administration of anti‐SDF‐1 or anti‐CXCR4 ablated Th17 cells in the bone marrow but did not affect Th17 precursor frequency in the lung. This was also associated with significant reductions in serum G‐CSF levels as well as a reduction in the increase in absolute neutrophils counts observed in the peripheral blood of infected animals given control antibody. The SDF‐1/CXCR4 axis is activated by KP lung infection and is required for Th17 cell recruitment to the bone marrow as well as controlling serum G‐CSF and increases in neutrophil counts. We postulate that Th17 cell use CXCR4 to home to sites of granulopoiesis.