Impact of Cutaneous IL-10 on Resident Epidermal Langerhans’ Cells and the Development of Polarized Immune Responses

Abstract

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-1β. 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-1β. 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.

Danger Signaling through the Inflammasome Acts as a Master Switch between Tolerance and Sensitization

“…These results are consistent with a previous report showing that IL-12 can turn DNTB into a strong sensitizer (14). IL-10 secretion, which antagonizes LC migration and IL-12 priming of T cells (28), was slightly higher in ASC deficient mice, but the difference was not statistically significant and the very low levels observed may undermine the relevance of our finding. Hence, our results suggest but do not prove that the inflammasome may modulate the secretion levels of IL-10, which may in turn regulate T cell fate.…”

Activation of Human Dendritic Cells byp-Phenylenediamine

“…Skinresident dendritic cells are potent antigen-presenting cells and immunological sentinels that respond following allergen exposure by functional maturation and migration toward draining lymph nodes (Cumberbatch et al, 2005). Dendritic cells exhibit a unique ability to activate naive T cells depending on their maturational stage.…”

The hair dyes PPD and PTD fail to induce a TH2 immune response following repeated topical application in BALB/c mice

“…More specifically, it may affect the antigen-presenting function of Langerhans cells and dendritic cells, since IL-10 pre-treatment of antigen-presenting cells was found to promote T H 2 cell activation (De Smedt et al, 1997;Morel et al, 1997). Cumberbatch et al (2005) demonstrated that chemical contact allergens and respiratory allergens exert differential effects on the kinetics of Langerhans cell activation and migration as a result of a differential cutaneous induction of IL-10. They concluded that immediate-type allergens may induce a cytokine environment that promotes the activation of dendritic cells with the ability to drive a T H 2-type immune response that may lead to an immediate-type allergy.…”