Impaired T cell activation and increased Th2 lineage commitment in Annexin-1-deficient T cells.
Annexin-1 is a well-known endogenous anti-inflammatory protein that modulates the activation of cells of the innate immune system such as neutrophils and macrophages. We have recently reported a positive role for the exogenous protein on T cell differentiation, however, whether such a role holds true for the endogenous protein has yet to be determined. This aspect has been investigated here finding that Annexin-1-deficient T cells display an impaired activation and proliferation in response to anti-CD3 plus anti-CD28 stimulation. Furthermore, differentiation of T cells from Annexin-1-deficient mice in Th0/Th1/Th2 or Th17 skewing conditions demonstrated an increased Th2 phenotype compared to cells from control littermates. Similar results were obtained when we analyzed the Th1/Th2 profile of lymph node cells obtained from mice immunized with keyhole limpet hemocyanin or the inflammatory infiltrate in mouse model of allergic inflammation. These results demonstrate a novel modulatory role of endogenous Annexin-1 in TCR signaling and T cell differentiation and suggest this protein might play a dual and complementary role in the innate and adaptive immune response.
D'Acquisto
Fulvio
F
William Harvey Research Institute, Barts and The London, London, UK. F.Dacquisto@qmul.ac.uk
Paschalidis
Nikolaos
N
Sampaio
Andre L F
AL
Merghani
Ahmed
A
Flower
Roderick J
RJ
Perretti
Mauro
M
D000818:Animals; D017305:Annexin A1 / Q000172:deficiency*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*
D017305:Annexin A1