Impact of cutaneous IL-10 on resident epidermal Langerhans' cells and the development of polarized immune responses.
Prolonged topical exposure of BALB/c mice to chemical contact and respiratory allergens stimulates, respectively, preferential Th1- and Th2-type responses with respect to serum Ab isotype and cytokine secretion phenotypes displayed by draining lymph node cells. We now report that differential cytokine secretion patterns are induced rapidly in the skin following first exposure to the contact allergen 2,4-dinitrochlorobenzene (DNCB) and the respiratory sensitizer trimellitic anhydride (TMA). TMA induced early expression of IL-10, a cytokine implicated in the negative regulation of Langerhans cell (LC) migration, whereas exposure to DNCB resulted in production of the proinflammatory cytokine IL-1beta. Associated with this, TMA provoked LC migration with delayed kinetics compared with DNCB, and local neutralization of IL-10 caused enhanced LC mobilization in response to TMA with concomitant up-regulation of cutaneous IL-1beta. We hypothesize that these differential epidermal cytokine profiles contribute to the polarization of immune responses to chemical allergens via effects on the phenotype of activated dendritic cells arriving in the draining lymph node. Thus, TMA-exposed dendritic cells that have been conditioned in vivo with IL-10 (a potent inhibitor of the type 1-polarizing cytokine IL-12) are effective APCs for the development of a Th2-type response.
Cumberbatch
Marie
M
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, United Kingdom. marie.cumberbatch@syngenta.com
Clelland
Kirsty
K
Dearman
Rebecca J
RJ
Kimber
Ian
I
D000287:Administration, Topical; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D002465:Cell Movement; D016207:Cytokines / Q000096:biosynthesis; D004137:Dinitrochlorobenzene / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007509:Irritants / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D007700:Kinetics; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D012867:Skin / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D004137:Dinitrochlorobenzene; D007509:Irritants; D010796:Phthalic Anhydrides; D016753:Interleukin-10; C015559:trimellitic anhydride