Detection and localization of chemokine gene expression in autoimmune thyroid disease.
OBJECTIVE
Autoimmune thyroid disease (Hashimoto's thyroiditis and Graves' disease) is characterized by lymphocytic infiltration of the thyroid gland. Chemokines are cytokines with chemoattractant properties for a range of immune effector cells and might therefore play a significant role in the initiation and maintenance of the autoimmune process. The aim of this study was to analyse chemokine gene expression in autoimmune thyroid tissue and in cultured thyroid follicular cells (TFC).


METHODS
Immunocytochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR) amplification were used to analyse the expression of monocyte chemoattractant protein (MCP)-1, RANTES (regulated upon activation, normal T cell expressed and secreted), macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, interferon (IFN)-gamma-inducible protein (IP)-10 and monokine induced by IFN-gamma (Mig) in thyroid tissue from patients with Hashimoto's thyroiditis (n = 4), Graves' disease (n = 6) and nonautoimmune multinodular goitre (n = 4). Chemokine gene expression was also examined in cultured TFC by RT-PCR.


RESULTS
Expression of MCP-1, RANTES, MIP-1 alpha, MIP-1 beta, IP-10 and Mig was demonstrated in all Hashimoto's and most Graves' thyroid specimens but very little expression was detected in the nonautoimmune goitre samples. In thyroid tissue from Graves' disease patients, positive staining for chemokines was largely restricted to the lymphocytic cell infiltrate. Within thyroid tissue from Hashimoto's patients, there was evidence for the expression of all chemokines by thyroid follicular cells, suggesting a role for local chemokine synthesis by the glandular epithelial cells in the recruitment of inflammatory cells into the gland in autoimmunity. The present work also showed that expression all the chemokine genes analysed could be induced in cultured thyroid cells by IFN-gamma and interleukin (IL)-1 alpha. Expression of all the chemokines examined was not stimulated by TSH.


CONCLUSIONS
We postulate that TFC may play a role in the pathogenesis of autoimmune thyroid disease as they are able to express the chemokines MIP-1 alpha, MIP-1 beta, MCP-1, RANTES, IP-10 and Mig that would promote the infiltration of immune cells into the thyroid gland.
Kemp
E Helen
EH
Division of Clinical Sciences (North), University of Sheffield, Northern General Hospital, UK. e.h.kemp@sheffield.ac.uk
Metcalfe
Russell A
RA
Smith
Karen A
KA
Woodroofe
M Nicola
MN
Watson
Philip F
PF
Weetman
Anthony P
AP
D000328:Adult; D000368:Aged; D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000032:analysis / Q000235:genetics; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines / Q000235:genetics*; D019743:Chemokines, CXC / Q000032:analysis / Q000235:genetics; D006111:Graves Disease / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000737:chemistry / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology*
C080810:CXCL9 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger