Dendritic cells (DCs) are the fraction of immune cells that initiate immune responses in the body. Antigens are captured by DCs, processed, and transferred to T cells. Depending on the micro environmental cytokines around, antigen-pulsed DCs induce Th1 response or Th2 response or fulfill the immune tolerogenic functions [1]. A fraction of DCs produce IL-10 to induce type 1 regulatory T cells (Tr1 cells) or regulatory B cells (Bregs) [2]. This feature of DCs is called the tolerogenic capacity. This fraction of DCs is designated as tolerogenic DCs (TolDCs). It is recognized that the dysfunctional TolDCs are associated with numerous immune disorders, such as airway allergy and food allergy [[3], [4], [5]]. The underlying mechanism has not been fully comprehended yet. Remedies for restoring the functions of TolDCs are currently limited. Moreover, there is still a lack of understanding about the development and regulation of TolDCs.

Airway allergy (AA) is an adverse response to the innocent airborne antigens by the airway immune system. The mechanism that underlies AA is not clear. It is recognized that abnormal behaviors of nDC contribute to the pathogenesis of AA. For example, high levels of tripartite motif-containing protein 41 (Trim41, a ubiquitin E3 ligase) were found in DCs of an AA mouse model in a previous study [4], which induced degradation of c-Maf protein (the Il10 transcription factor) and compromised the tolerogenic capacity of DCs. On the other hand, epigenetic conditions, such as methylation, also regulate DC functions [6]. Gene transcription is facilitated by hypomethylation while it is hindered by hypermethylation. The effects of the abnormal epigenetic condition on the functions of tolerogenic DCs are still being investigated. Recent reports indicate that lysine-specific demethylase 4D (KDM4D) is an important factor in preventing targeted protein degradation, which can be upregulated by deubiquitinating enzyme 14 (USP14) [7]. It is necessary to investigate whether the KDM4D/USP14 signaling pathway is responsible for controlling the tolerogenic capacity of DCs in subjects with AA. The data of present study indicate that lower quantities of KDM4D/USP14 are lower in airway naïve DCs (nDCs) of mice with AA, which are associated with the impaired tolerogenic capacity of airway nDCs of AA mice.