Role for interferon-gamma inducible chemokines in endocrine autoimmunity: an expanding field.
The chemoattractant cytokines (chemokines) have been classified into 4 major sub-families in relation to the position of the cysteine residues in their NH2 terminal portion. Interferon-gamma inducible chemokines (CXCL9/Mig, CXCL10/IP-10, CXCL11/I-TAC), strongly associated to Th1-mediated immune responses, belong to the CXC sub-family. They represent an exception among chemokines in that they specifically interact with a single type of receptor, named CXCR3. A statistically significant increase of CXCL10/IP-10 and CXCL9/Mig expression, in thyroid tissue specimens obtained from subjects affected by Hashimoto's thyroiditis and recent onset Graves' disease has been reported. Furthermore, a statistically significant increase in serum CXCL10/IP-10 levels has been found in newly diagnosed Graves' patients when compared to healthy subjects as well as patients with long standing disease and a strong statistically significant inverse correlation between circulating CXCL10/IP-10 levels and disease duration has been demonstrated. Similar findings have been obtained when Type 1 autoimmune diabetes affected patients have been taken into account. In conclusion, such experiences have demonstrated an important role played by interferon-gamma inducible CXC chemokines in the pathogenesis of glandular autoimmunity. In fact, it is reasonable to assume that glandular epithelial cells may modulate the autoimmune process at least in its initial phase, through the production of chemokines which induce migration of Th1 lymphocytes into the gland. Interferon-gamma secretion by lymphocytes would, in turn, stimulate chemokines production by follicular cells, thus perpetuating the autoimmune cascade.
Rotondi
M
M
Department of Clinical and Experimental Medicine F. Magrassi, II University of Naples, Naples, Italy.
Lazzeri
E
E
Romagnani
P
P
Serio
M
M
D015551:Autoimmunity / Q000276:immunology*; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000276:immunology*; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma