Eosinophils infiltrate thyroids, but have no apparent role in induction or resolution of experimental autoimmune thyroiditis in interferon-gamma(-/-) mice.
Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by mouse thyroglobulin (MTg)-sensitized splenocytes activated with MTg and interleukin (IL)-12. Our previous studies showed that, when used as donors and recipients, interferon (IFN)-gamma(-/-) and wild-type (WT) DBA/1 mice both develop severe G-EAT. Thyroid lesions in IFN-gamma(-/-) mice have many eosinophils and few neutrophils, while those in WT mice have extensive neutrophil infiltration and few eosinophils. Thyroid lesions in IFN-gamma(-/-) mice consistently resolve by day 40-50, whereas those in WT mice have ongoing inflammation and fibrosis persisting for more than 60 days. To determine if the extensive infiltration of eosinophils in thyroids of IFN-gamma(-/-) mice contributes to thyroid damage and/or early resolution of G-EAT, anti-IL-5 was used to inhibit migration of eosinophils to thyroids. G-EAT severity was compared at day 20 and day 40-50 in IFN-gamma(-/-) recipients given anti-IL-5 or control immunoglobulin G (IgG). Thyroids of anti-IL-5-treated IFN-gamma(-/-) mice had few eosinophils and more neutrophils at day 20, but G-EAT severity scores were comparable to those of control IgG-treated mice at both day 20 and day 40-50. Expression of chemokine (C-X-C motif) ligand 1 (CXCL1) mRNA was higher and that of chemokine (C-C motif) ligand 11 (CCL11) mRNA was lower in thyroids of anti-IL-5-treated IFN-gamma(-/-) mice. IL-5 neutralization did not influence mRNA expression of most cytokines in IFN-gamma(-/-) mice. Thus, inhibiting eosinophil migration to thyroids did not affect G-EAT severity or resolution in IFN-gamma(-/-) mice, suggesting that eosinophil infiltration of thyroids occurs as a consequence of IFN-gamma deficiency, but these cells have no apparent pathogenic role in G-EAT.
Fang
Yujiang
Y
Department of Internal Medicine, University of Missouri School of Medicine, Columbia, MO, USA. fangy@health.missouri.edu
Chen
Kemin
K
Jackson
Daniel A
DA
Sharp
Gordon C
GC
Braley-Mullen
Helen
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D054413:Chemokine CCL11 / Q000235:genetics; D054360:Chemokine CXCL1 / Q000235:genetics; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D005355:Fibrosis; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013974:Thyroxine / Q000097:blood
D000911:Antibodies, Monoclonal; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D020381:Interleukin-17; D015848:Interleukin-5; D016753:Interleukin-10; D007371:Interferon-gamma; D013954:Thyroglobulin; D013974:Thyroxine