Expression of IP-10/CXCL10 and MIG/CXCL9 in the thyroid and increased levels of IP-10/CXCL10 in the serum of patients with recent-onset Graves' disease.
Both mRNA and protein expression of the chemokines IP-10/CXCL10 and Mig/CXCL9, as well as of their receptor, CXCR3, were assessed in the thyroid glands of 16 patients suffering from Graves' disease (GD). In addition, IP-10/CXCL10 levels were measured in the serum of 50 GD patients. Expression of IP-10/CXCL10, Mig/CXCL9, and CXCR3 was poor or absent in normal thyroid tissue from patients undergoing thyroidectomy because of primary localized thyroid tumors, while both the chemokines and their receptor were present in most thyroid glands of patients affected by GD. IP-10/CXCL10 and Mig/CXCL9 localized to infiltrating lymphocytes and macrophages, as well as to resident epithelial follicular cells, whereas CXCR3 was mainly found at the level of infiltrating inflammatory cells and endothelial cells from large and small vessels. Of note, maximal expression of IP-10/CXCL10 and Mig/CXCL9 was found in the thyroid gland of patients with recent-onset GD and was correlated with interferon (IFN)-gamma. Accordingly, high levels of IP-10/CXCL10 could be measured in the serum of patients with short-duration GD. Taken together, the results of this study demonstrate that the CXCR3-binding chemokines IP-10/CXCL10 and Mig/CXCL9 play an important role in the recruitment of cells and in the amplification of inflammation in GD. They also suggest that the production of these chemokines by resident follicular epithelial cells may contribute to the recruitment of CXCR3-expressing type 1 T-helper cells in the initial phases of GD.
Romagnani
Paola
P
Department of Clinical Pathophysiology, University of Florence, Florence, Italy. promagnani@iol.it
Rotondi
Mario
M
Lazzeri
Elena
E
Lasagni
Laura
L
Francalanci
Michela
M
Buonamano
Andrea
A
Milani
Stefano
S
Vitti
Paolo
P
Chiovato
Luca
L
Tonacchera
Massimo
M
Bellastella
Antonio
A
Serio
Mario
M
D000328:Adult; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006111:Graves Disease / Q000097:blood / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma