Neutrophil myeloperoxidase regulates T cell-driven tissue inflammation in mice by inhibiting dendritic cell function

Dragana Odobasic, A. Richard Kitching, Yuan Yang, Kim M. O'Sullivan, Ruth C.M. Muljadi, Kristy L. Edgtton, Diana S.Y. Tan, Shaun A. Summers, Eric F. Morand and Stephen R. Holdsworth

Key points

  • MPO, via its catalytic activity, inhibits the generation of adaptive immunity by suppressing DC function.

  • MPO-mediated inhibition of adaptive immunity attenuates T cell-driven tissue inflammation.


Myeloperoxidase (MPO) is important in intracellular microbial killing by neutrophils, but extracellularly, causes tissue damage. Its role in adaptive immunity and T cell-mediated diseases is poorly understood. Here, T cell responses in lymph nodes (LNs) were enhanced by MPO deletion or in vivo inhibition, causing enhanced skin delayed type hypersensitivity and antigen-induced arthritis. Responses of adoptively-transferred OT-II T cells were greater in MPO-deficient than wildtype recipients. MPO, deposited by neutrophils in LNs after antigen injection, interacted with dendritic cells (DCs) in vivo. Culture of murine or human DCs with purified MPO or neutrophil supernatant showed that enzymatically-dependent MPO-mediated inhibition of DC activation occurs via MPO-generated reactive intermediates and involves DC Mac-1. Transfer of DCs cultured with wildtype, but not MPO-deficient, neutrophil supernatant attenuated antigen-specific immunity in vivo. MPO deficiency or in vivo inhibition increased DC activation in LNs after immunisation. Studies with DQ-ovalbumin showed that MPO inhibits antigen uptake/processing by DCs. In vivo DC transfer and in vitro studies showed that MPO inhibits DC migration to LNs by reducing their expression of CCR7. Therefore, MPO, via its catalytic activity, inhibits the generation of adaptive immunity by suppressing DC activation, antigen uptake/processing and migration to LNs, to limit pathological tissue inflammation.

  • Submitted September 14, 2012.
  • Accepted February 4, 2013.