Functional role of thymic stromal lymphopoietin in chronic allergic keratoconjunctivitis.
OBJECTIVE
Previous reports have shown that thymic stromal lymphopoietin (TSLP) plays a role in atopic diseases. This study was undertaken to investigate the expression of TSLP in the giant papillae obtained from patients with vernal keratoconjunctivitis (VKC) or atopic keratoconjunctivitis (AKC), and its functional roles were analyzed.


METHODS
TSLP mRNA expression was examined in resected conjunctival samples obtained from four patients with VKC/AKC and three control subjects by reverse transcription-polymerase chain reaction. Anti-TSLP, anti-dendritic cell-limbic system-associated membrane protein (anti-DC-LAMP), and anti-tryptase immunohistochemical staining was performed with 10 resected giant papillae. Human conjunctival epithelial (HCJE) cells were stimulated with poly I:C, with and without endosomal inhibitor, to examine TSLP mRNA expression. Cultured human mast cells were stimulated with recombinant (r)TSLP to analyze the downstream effect of TSLP.


RESULTS
All four VKC/AKC samples showed TSLP mRNA expression; however, no TSLP mRNA expression was found in the control conjunctivae. Anti-TSLP immunohistochemical staining showed preferential expression in the epithelial cells and some infiltrated cells of the giant papillae, but not in the control conjunctivae. Double immunohistochemical staining with TSLP and DC-LAMP or tryptase showed the existence of activated dendritic cells and mast cells near TSLP-positive cells in the giant papillae. Real-time PCR analysis showed that poly I:C induced TSLP mRNA expression in HCJEs in an endosomal-function-dependent manner and that rTSLP could induce IL-13 mRNA expression in the mast cells synergistically with IL-33.


CONCLUSIONS
The TSLP protein produced in conjunctival epithelial cells plays a role in severe ocular allergy through the activation of dendritic cells and mast cells in synergy with other cytokines.
Matsuda
Akira
A
Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan. akimatsu@juntendo.ac.jp
Ebihara
Nobuyuki
N
Yokoi
Norihiko
N
Kawasaki
Satoshi
S
Tanioka
Hidetoshi
H
Inatomi
Tsutomu
T
de Waal Malefyt
Rene
R
Hamuro
Junji
J
Kinoshita
Shigeru
S
Murakami
Akira
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002648:Child; D002908:Chronic Disease; D003233:Conjunctivitis, Allergic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D000067596:Interleukin-33; D015851:Interleukin-7 / Q000235:genetics; D007378:Interleukins / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology; D053802:Tryptases / Q000378:metabolism; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
D015816:Cell Adhesion Molecules, Neuronal; D016207:Cytokines; D058851:GPI-Linked Proteins; C506536:IL33 protein, human; C508605:IL7 protein, human; D000067596:Interleukin-33; D015851:Interleukin-7; D007378:Interleukins; D018942:Macrolides; D012333:RNA, Messenger; C095362:limbic system-associated membrane protein; C057620:bafilomycin A; D053802:Tryptases; D011070:Poly I-C; D000094632:Thymic Stromal Lymphopoietin