The immune imbalance of Treg/Th17 in secretory otitis media patients may
be related to PI3K/Akt/mTOR signaling activation in the middle ear
mucosa
Abstract
Objective: To assess whether secretory otitis media may be caused by
immune imbalance of Treg/Th17 mediated by PI3K/Akt/mTOR signaling, so as
to find new therapeutic target. Methods: IL-17, TGF- and IL-6, IL-10 and
Th17 cytokines were detected in peripheral blood of OME patients (PC
group) and healthy people (NC group) by ELISA. The expression of ROR t
mRNA and Foxp3mRNA in PBMC was detected by RT-PCR. OME rat model was
established and the changes of lymphocytes in middle ear mucosa and
spleen and PI3K/Akt/mTOR signaling in middle ear mucosa were detected by
HE staining, IHC, WB and flow cytometry. Results: The immune imbalance
of Treg/Th17 in secretory otitis media (OME) was confirmed by the
expression of cytokines in OME serum and analysis of ROR T and Foxp3
mRNA which was Th17 and Treg specific transcription respectively. OME
rat model further confirmed that Treg/Th17 imbalance could lead to OME
as demonstrated by staining of MIDDLE ear mucosa and expression of ROR T
and Foxp3. PI3K, Akt, and mTOR proteins were expressed in the MIDDLE ear
mucosa of OME group and CON group, respectively. Compared with CON
group, the expression of P-MTOR and P-PI3K proteins in the middle ear
mucosa of OME group was significantly increased. Conclusions: Treg/Th17
imbalances are found in OME patients and OME animal model and the
pathogenic mechanism may be due to systemic abnormal immune response,
activated PI3K/Akt/mTOR signaling, abnormal T cell differentiation,
leading to middle ear mucosal hyperemia, edema and subsequent occurrence
of OME.