title: Chemokine expression during development of fibrosis versus resolution in a murine model of granulomatous experimental autoimmune thyroiditis.
abstract: Severe granulomatous experimental autoimmune thyroiditis (G-EAT) in DBA/1 or CBA/J wild type (WT) mice at day 19 progresses to fibrosis by day 35, but severe G-EAT in DBA/1 interferon (IFN)-gamma-/- mice or less-severe G-EAT at day 19 in WT mice resolves by day 35. To study the role of chemokines in autoimmune diseases and fibrosis, profiles of chemokines and chemokine receptors were analyzed in DBA/1 WT versus IFN-gamma-/- and CBA/J thyroids, which have distinct outcomes of autoimmune inflammation. Gene expression of CXC chemokine ligand 1 (CXCL1) and CXC chemokine receptor 2 (CXCR2) paralleled neutrophil infiltration and thyrocyte destruction in DBA/1 WT or CBA/J thyroids, and gene expression of CC chemokine ligand 11 (CCL11), CCL8, and CC chemokine receptor 3 paralleled eosinophil infiltration in IFN-gamma-/- thyroids. Gene and protein expression of CXCL10, CXCL9, and CXCR3 was significantly lower in IFN-gamma-/- compared with DBA/1 WT thyroids. Moreover, immunostaining showed that CXCL10 was expressed by thyrocytes and inflammatory cells, and strong expression of CXCL10 by thyrocytes was as early as day 7. High expression of CCL2 was only observed in severely destroyed DBA/1 WT or CBA/J thyroids, which would develop fibrosis. Thus, the differential expression of chemokines may direct distinct cellular populations in DBA/1 WT versus IFN-gamma-/- thyroids. Up-regulation of CXCL10 by thyrocytes suggests its role in regulating the recruitment of specific subsets of activated lymphocytes to the thyroid during autoimmune inflammation. The early expression of CXCL1, CXCL10, and CCL2 may suggest their involvement in the initiation and perpetuation of disease in severe G-EAT thyroids, which progress to fibrosis.
authors.affiliation: Department of Medicine, University of Missouri, M306 Medical Sciences, One Hospital Dr., Columbia, MO 65212, USA. Chenk@health.missouri.edu
authors.forename: Kemin
authors.initials: K
authors.lastname: Chen
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Wei
authors.forename: Adam
authors.initials: A
authors.lastname: Alter
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Sharp
authors.forename: Helen
authors.initials: H
authors.lastname: Braley-Mullen
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013968:Thyroiditis, Subacute / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D018925:Chemokines; D007371:Interferon-gamma