The Immunomodulatory Effect Of IRAK-M In Dust Mite-induced Asthma And The Clinical Characteristics Of Patients With Eosinophilic Lung Disease

Object:In this investigation,we studied the effect and mechanism of IRAK-M on lung inflammation induced by HDM using IRAK-M knockout mice.Method:asthma model:acute asthma model were established in IRAK-M KO and wild type mice through HDM sensitization and challenge;IRAK-M expression in wild type mice was evaluated by qRT-PCR and immunohistochemistry.Specific airway resistance(sRaw)was measured by using a double-flow plethysmograph.To evaluate the lung inflammation by HE staining.Lung sections were stained with alcian blue/periodic acid-Schiff to identify mucus-containing cells,stained with Masson trichrome staining to assess fibrosis deposition around bronchi and vessels,stained with a-smooth muscle actin(a-SMA)to evaluate smooth muscle hyperplasia;To determine the cytokines,transcription factors by ELISA or qRT-PCR.To count the number or classification of inflammatory cells,co-stimulatory molecules on Mac and DCs,and antigen uptake of Mac in BALF by flow cytometry.To detect immunoglobulin in serum by ELISA.Results:1)IRAK-M expression was significantly elevated in the lung of asthma;2)Airway resistance:Compared with PBS groups,Raw was increased in HDM groups,however,it was not significantly elevated in KO mice relative to WT mice after exposure to HDM.3)Lung morphology:we observed epithelial damage,bronchial wall thickening,mucus secretion,inflammatory cells infiltration in the HDM groups;KO mice showed more serious lung inflammation after HDM insult.4)Inflammation cells in BALF:the number of total cells were increased in HDM groups compared to PBS groups,but there was no significantly difference between KO-HDM mice and WT-HDM mice;percentages of eosinophils,Th2 cells,B cells in KO-HDM group were increased than those in WT-HDM group.5)Expression of cytokines in BALF or lung:compared with WT-HDM group,proteins expression in BALF of IL-4,IL-5,IL-13,IFN-y,IL17A,and epithelial cells associated factors IL-25,IL-33,TSLP were increased in KO-HDM group;mRNA of IL-4 in KO-HDM lung was highly expressed than it in WT-HDM mice.6)mRNA of T cell subsets transcription factors:the mRNA expression of Treg-Foxp3 were decreased and Th2-Gata were increased in KO mice than those in WT mice after HDM exposure.7)Immunoglobulin in serum:levels of total IgE,HDM-specific IgE and IgGl were increased in HDM groups,and the levels of these proteins were more higher in KO mice than WT mice.8)Airway remodeling:HDM insult induced significant airway remodeling in both WT and KO mice;airway goblet cell hyperplasia and smooth muscle hyperplasia were more serious in KO mice than WT mice after HDM insult.9)Expression of co-stimulatory molecules on BALF Mac and DCs:There was significantly up-regulation of molecules OX40L,CD80 and down-regulation of CD 124 on BALF Mac from KO mice compared to WT mice after HDM exposure.10)Antigen uptake of Mac:the antigen uptake capacity of BALF Mac in KO mice was decreased than WT mice after exposure to HDM.Conclusion:IRAK-M were significantly elevated in lung of HDM induced asthma,and loss of IRAK-M could aggravate airway inflammation and remodeling,probably through affecting antigen uptake,expression of co-stimulatory molecules of Mac and CD4+T cells differentiation.Objective:To summarize the clinical features of eosinophilic lung diseases(ELD).Methods:We retrospectively analyzed the clinical manifestations,laboratory findings,accessory examination results,and pathology of 40 patients who were diagnosed with ELD and hospitalized in Peking Union Medical College Hospital from January 2013 to December 2016.Results:There were 19 males and 21 females,and the average age was(48.58±18.25)years.The diagnoses included ABPA(n=20),EGPA(also known as Churg-Strauss syndrome,CSS)(n=10),CEP(n=8),parasitic infection(n=1),and drug-induced eosinophilic pneumonia(n=1).EOS counts in peripheral blood were increased in 35 patients(87.5%),and EOS counts in BALF increased in 17 of 18 patients(94.4%).Arterial blood gas analysis showed varying degrees of hypoxemia in 23 patients(57.5%),pulmonary function tests showed ventilatory dysfunction in 27 patients(67.5%),and defect in diffusion capacity in 12 patients(30.0%).Chest CT revealed bilateral flaky,streaky or diffuse ground-glass infiltrates and consolidations;in addition,central cylindrical bronchiectasis and mucous plugging with "finger-in-glove"pattern were seen in patients with ABPA.Diffuse EOS infiltration was revealed in lung or other tissue biopsy.Glucocorticoids alone or combined with other therapies were effective in most patients.Conclusions:ELD has a wide range of clinical presentations,and can easily be misdiagnosed.Increased EOS count in peripheral blood and BALF combined with infiltration manifestations in chest imaging are helpful for the diagnosis of ELD.Oral administration of glucocorticoids is the primary therapy for ELD.