Food allergy can influence the development of
colorectal cancer, although the underlying mechanisms are unclear. While mast cells (MC) store and secrete
histamine, immature myeloid cells (IMC) are the major site of
histidine decarboxylase (HDC) expression, the
enzyme responsible for
histamine production. From our earlier work, we hypothesized that
histamine is central to the association between
allergy and colorectal
carcinogenesis through its influence on the MC-MDSC axis. Here, we show that in wild type (WT) mice,
ovalbumin (OVA) immunization elicits a typical TH2 response. In contrast, in HDC-/- mice, the response to OVA
allergy is skewed towards infiltration by
IL-17 expressing MCs. This response is inhibited by
histamine treatment. The HDC-/- allergic IL-17-expressing MCs promote MDSC proliferation and upregulation of Cox-2 and Arg-1. OVA
allergy in HDC-/- mice increases the growth of colon
tumor cells in both the MC38
tumor cell implantation model and the AOM/DSS
carcinogenesis model. Taken together, our results show that
histamine represses IL-17-expressing MCs and their subsequent activation of MDSCs, attenuating the risk of
colorectal cancer in the setting of
food allergy. Targeting the MC-MDSC axis may be useful for
cancer prevention and treatment in patients, particularly in those with
food allergy.