Low Zone Tolerance Requires ICAM-1 Expression to Limit Contact Hypersensitivity Elicitation

Abstract

Painting subsensitizing doses of contact sensitizers on skin (low-dose tolerization) induces antigen (Ag)-specific tolerance, known as low zone tolerance (LZT), which has been experimentally demonstrated by the inhibition of contact hypersensitivity (CHS). Although LZT resulted from the inhibition of the sensitization phase, the effects on the effector/elicitation phase remain unknown. L-selectin and ICAM-1 regulate leukocyte influx into inflamed tissues during the elicitation phase of CHS. LZT was investigated in mice lacking either L-selectin or ICAM-1 to evaluate the roles these leukocyte receptors play in LZT during the elicitation phase. Low-dose tolerization effectively suppressed CHS in wild-type and L-selectin-deficient mice, but not in ICAM-1-deficient mice. Low-dose-tolerized ICAM-1-deficient splenocytes effectively suppressed the elicitation phase in naive wild-type recipients. Sensitized ICAM-1-deficient splenocytes showed normal proliferative responses to the sensitizing Ag and generated normal CHS in wild-type recipients. Thus, ICAM-1 deficiency did not affect sensitization. LZT was associated with a lack of ICAM-1 upregulation after elicitation, suggesting a potentially mechanistic role for ICAM-1. The blockade of IL-10, a possible mediator of LZT, produced by hapten-specific suppressor cells, abrogated LZT and restored ICAM-1 upregulation. These results indicate that low-dose tolerization controls CHS by abrogating ICAM-1 upregulation during the elicitation phase.

Immune-Regulatory and Molecular Effects of Antidepressants on the Inflamed Human Keratinocyte HaCaT Cell Line

“…Likewise, the use of anti-ICAM-1 or anti-LFA-1 (ICAM-1 ligand) antibodies inhibits the rolling process and migration of T lymphocytes to local lymph nodes during an ongoing inflammatory response (Teijeira et al 2017 ). Moreover, tolerance to low doses of allergens applied to the skin of mice was associated with the abolition of elevated ICAM-1 expression in the effector phase of the CHS reaction (Komura et al 2009 ). We observed that all antidepressants lowered ICAM-1 gene expression.…”