Early production of thymic stromal lymphopoietin precedes infiltration of dendritic cells expressing its receptor in allergen-induced late phase cutaneous responses in atopic subjects.
BACKGROUND
Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that triggers dendritic cell-mediated T helper (Th)2 inflammatory responses through a receptor consisting of a heterodimer of the IL-7 receptor alpha (IL-7Ralpha) chain and the TSLP receptor (TSLPR), which resembles the cytokine receptor common gamma chain. Dendritic cells activated by TSLP prime development of CD4(+) T cells into Th2 cells contributing to the pathogenesis of allergic inflammation. We hypothesized that allergen exposure induces expression of TSLP and results in recruitment of TSLPR bearing cells in the cutaneous allergen-induced late-phase reaction (LPR) in atopic subjects.


METHODS
Skin biopsies were obtained from atopic subjects (n = 9) at various times after cutaneous allergen challenge. In situ hybridization and immunohistochemistry were used to determine TSLP mRNA expression and to measure infiltration of TSLPR(+) DC in skin LPR. RT-PCR and flow cytometry were employed to analyse TSLPR expression on isolated blood DC.


RESULTS
Allergen-induced skin TSLP expression occurred as early as 1 h after allergen challenge, whereas TSLPR(+) and CD11c(+) cells infiltrated relatively late (24-48 h). The majority of TSLPR(+) cells were DC co-expressing blood DC antigen-1 (BDCA-1) or BDCA-2. Freshly isolated blood DC expressed both TSLPR and IL-7Ralpha chains. Maturation and stimulation with TSLP or polyriboinosinic-polyribocytidylic acid in vitro upregulated the expression of both TSLPR and IL-7Ralpha chains in DC but not in chemoattractant receptor-homologous molecule expressed on Th2 cells(+) CD4(+) T cells.


CONCLUSIONS
The data suggest that TSLP plays a role in augmenting, through DC recruitment and activation, the development of Th2-type T cells in allergic inflammation.
Corrigan
C J
CJ
MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Division of Asthma, Allergy & Lung Biology, Guy's Hospital, King's College London, London UK.
Jayaratnam
A
A
Wang
Y
Y
Liu
Y
Y
de Waal Malefyt
R
R
Meng
Q
Q
Kay
A B
AB
Phipps
S
S
Lee
T H
TH
Ying
S
S
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D018949:Antigens, CD1; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006023:Glycoproteins; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007369:Interferon Inducers / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D011070:Poly I-C / Q000494:pharmacology; D018121:Receptors, Cytokine / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000473:pathology; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
D000485:Allergens; D018949:Antigens, CD1; D000954:Antigens, Surface; C437944:CD1C protein, human; C443299:CLEC4C protein, human; C498762:CRLF2 protein, human; D016207:Cytokines; D006023:Glycoproteins; C508605:IL7 protein, human; D007369:Interferon Inducers; D019409:Interleukin-15; D015851:Interleukin-7; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D011070:Poly I-C; D000094632:Thymic Stromal Lymphopoietin