Contribution of IL-33 to induction and augmentation of experimental allergic conjunctivitis.
IL-33, a member of the IL-1 family of cytokines, is the ligand for ST2 (IL-33Ralpha chain). IL-33 has the capacity to induce T(h)2 cytokine production from T(h)2 cells, mast cells and basophils, indicating that IL-33 has the potential to induce T(h)2 cytokine-mediated allergic inflammation of the eye. Thus, we tested the pathological role of IL-33 in allergic conjunctivitis (AC). As reported elsewhere, animals immunized with ragweed pollen (RW)/alum and boosted with RW/PBS developed AC promptly (within 15 min) and conjunctival eosinophilic inflammation after a delay (within 24 h) in response to eye drop challenge with RW. Furthermore, RW-immunized mice, when topically challenged with both RW and IL-33, developed more striking eosinophilia in their conjunctiva without exacerbation of the clinical AC score. This in vivo IL-33 treatment significantly increased the capacity of T cells in the cervical lymph nodes of RW-immunized mice to produce IL-4, IL-5 and IL-13 upon challenge with anti-CD3 and anti-CD28 antibodies in vitro. Furthermore, the infiltrating cells were largely eosinophils and a small proportion of CD4(+) T cells, both of which express ST2. We also found that even splenic eosinophils express ST2 and show increased expression in response to IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-33. Eosinophils, stimulated with IL-5 and/or GM-CSF, are responsive to IL-33, which induces production of IL-4 and chemokines. Finally, we showed that conjunctival tissues constitutively express biologically active IL-33, suggesting that IL-33 might play a crucial role in the induction and augmentation of AC.
Matsuba-Kitamura
Saori
S
Department of Immunology and Medical Zoology, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.
Yoshimoto
Tomohiro
T
Yasuda
Koubun
K
Futatsugi-Yumikura
Shizue
S
Taki
Yuuko
Y
Muto
Taichiro
T
Ikeda
Tomohiro
T
Mimura
Osamu
O
Nakanishi
Kenji
K
D000534:Alum Compounds / Q000008:administration & dosage; D031164:Ambrosia; D000818:Animals; D052179:Antigens, Plant / Q000008:administration & dosage / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003228:Conjunctiva / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004802:Eosinophilia; D006801:Humans; D007117:Immunization, Secondary; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D011058:Pollen / Q000276:immunology; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*
D000534:Alum Compounds; D052179:Antigens, Plant; D016207:Cytokines; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; C041524:aluminum sulfate