TLR2 agonist ameliorates murine experimental allergic conjunctivitis by inducing CD4 positive T-cell apoptosis rather than by affecting the Th1/Th2 balance.
Innate immune responses that operate through Toll-like receptors (TLRs) are actively involved in the development of diseases predominantly mediated by adaptive immune responses. This is true also for allergic disease, as TLRs have been found to be involved in the development of allergic airway inflammation. We investigated whether stimulating TLR2 also abrogates murine allergic conjunctivitis by upregulating Th1 responses. We found that treating mice during the efferent phase with the TLR2 agonist Pam3CSK4 significantly suppressed eosinophil infiltration into the conjunctiva. However, Pam3CSK4 treatment inhibited both the Th1 and Th2 responses in the mice, and also suppressed eosinophil infiltration in IFN-gamma knockout mice. Flow cytometric analysis demonstrated that Pam3CSK4 treatment significantly elevated the numbers of annexin V-positive splenocytes, especially CD4 positive T cells. Thus, the stimulation of TLR2 during the efferent phase of murine allergic conjunctivitis suppresses eosinophil infiltration by inducing CD4 positive T-cell apoptosis rather than upregulating Th1 responses.
Fukushima
Atsuki
A
Department of Ophthalmology, Kochi Medical School, Japan. fukusima@med.kochi-u.ac.jp
Yamaguchi
Tomoko
T
Ishida
Waka
W
Fukata
Kazuyo
K
Ueno
Hisayuki
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D055666:Lipopeptides; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000008:administration & dosage*; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000276:immunology*; D016896:Treatment Outcome
D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D010455:Peptides; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2