Chemokines determine local lymphoneogenesis and a reduction of circulating CXCR4+ T and CCR7 B and T lymphocytes in thyroid autoimmune diseases.
Chemokines and their corresponding receptors are crucial for the recruitment of lymphocytes into the lymphoid organs and for its organization acting in a multistep process. Tissues affected by autoimmune disease often contain ectopic lymphoid follicles which, in the case of autoimmune thyroid disorders, are highly active and specific for thyroid Ags although its pathogenic role remains unclear. To understand the genesis of these lymphoid follicles, the expression of relevant cytokines and chemokines was assessed by real time PCR, immunohistochemistry and by in vitro assays in autoimmune and nonautoimmune thyroid glands. Lymphotoxin alpha, lymphotoxin beta, C-C chemokine ligand (CCL) 21, CXC chemokine ligand (CXCL) 12, CXCL13, and CCL22 were increased in thyroids from autoimmune patients, whereas CXCL12, CXCL13, and CCL22 levels were significantly higher in autoimmune glands with ectopic secondary lymphoid follicles than in those without follicles. Interestingly, thyroid epithelium produced CXCL12 in response to proinflammatory cytokines providing a possible clue for the understanding of how tissue stress may lead to ectopic follicle formation. The finding of a correlation between chemokines and thyroid autoantibodies further suggests that intrathyroidal germinal centers play a significant role in the autoimmune response. Unexpectedly, the percentage of circulating CXCR4(+) T cells and CCR7(+) B and T cells (but not of CXCR5) was significantly reduced in PBMCs of patients with autoimmune thyroid disease when they were compared with their intrathyroidal lymphocytes. This systemic effect of active intrathyroidal lymphoid tissue emerges as a possible new marker of thyroid autoimmune disease activity.
Armengol
Maria-Pilar
MP
Laboratory of Immunobiology for Research and Application to Diagnosis, Center for Transfusion and Tissue Bank, Badalona, Spain.
Cardoso-Schmidt
Cristina B
CB
Fernández
Marco
M
Ferrer
Xavier
X
Pujol-Borrell
Ricardo
R
Juan
Manel
M
D001323:Autoantibodies / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000097:blood; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054422:Chemokine CCL22; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D018925:Chemokines / Q000097:blood / Q000502:physiology*; D019742:Chemokines, CC / Q000096:biosynthesis / Q000097:blood; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000097:blood / Q000502:physiology; D015536:Down-Regulation / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D038041:Lymphopoiesis / Q000276:immunology*; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000378:metabolism; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000378:metabolism; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D001323:Autoantibodies; C515482:CCL22 protein, human; C515370:CCR7 protein, human; D017252:CD3 Complex; C515255:CXCL12 protein, human; C110663:CXCL13 protein, human; D054422:Chemokine CCL22; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; C505886:LTB protein, human; C505697:LTBR protein, human; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D018124:Receptors, Tumor Necrosis Factor; D007371:Interferon-gamma