ILC3-like ILC2 subset increases in minimal persistent inflammation after acute type II inflammation of allergic rhinitis and inhibited by Biminkang: Plasticity of ILC2 in minimal persistent inflammation.

Minimal persistent inflammation (MPI), the local inflammation that occurs after an acute type II immune response in patients with allergic rhinitis (AR), is responsible for airway hyperreactivity and the recurrence of AR. Innate lymphoid cells (ILCs) play a crucial role in mucosal immune homeostasis, but the changes of ILC subsets in the MPI stage remain unclear. In this study, the levels of ILC-secreting cytokines in nasal lavages were analyzed from 19 AR patients and 8 healthy volunteers. AR and MPI model mice were established to study the ILC subsets. The results showed that IL-17A was significantly increased in nasal lavage of AR patients in the MPI stage by MSD technology. When compared with the AR model mice, the frequency of IL-13+ ILC2 in the nasal mucosa and lungs decreased, while IL-5+ ILC2 remain high in MPI model mice. A part of the IL-5+ ILC2 subset displayed ILC3-like characteristics with elevated RORγt, IL-17A and IL-23R expression. Especially, these ILC3-like ILC2 exhibited up-regulation of GATA3+ RORγt+ were increased in MPI model mice. After the treatment of Biminkang, the frequencies of IL-5+ ILC2, IL-17A+ ILC3, and GATA3+ RORγt+ ILC3-like ILC2 were significantly reduced, and IL-23R expression was also decreased on ILC3-like-ILC2 subset. These results suggested that the elevated IL-17A in the MPI stage has been related to or at least partly due to the increased of ILC3-like ILC2. Biminkang could effectively decrease IL-17A+ ILC3 and inhibit ILC3-like ILC2 subset in the MPI stage. Biminkang is effective in administrating MPI by regulating airway ILC homeostasis.

[Congenital Fibrinogen Deficiency Caused by Novel FGG Gene Mutation].

OBJECTIVE: To detect and analyze coagulation related indexes and genotypes of a patient with congenital fibrinogen deficiency and his family members, and to investigate the possible molecular pathogenesis. METHODS: Four peripheral blood samples (proband and 3 family members) were collected and the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fg), D-Dimer and eight coagulation factor indicators were detected. All exons and flanking sequences of the FGA, FGB, and FGG genes encoding the three peptide chains of fibrinogen were sequenced and analyzed by bioinformatics. RESULTS: Among the eight coagulation factors of the proband and the elder sister, F Ⅴ and F Ⅷ were slightly higher, TT was significantly prolonged, and Fg was significantly reduced. Sequencing results showed that c.901C>T heterozygous mutation existed in the FGG gene. Bioinformatics analysis showed that the mutation changed the original protein structure and reduced the number of hydrogen bonds. CONCLUSION: The fibrinogen gamma chain c.901C>T heterozygous mutation is the main cause of congenital fibrinogen deficiency in this family. This mutation is reported for the first time at home and abroad.

[Effect of modified zuoguiwan on Th17/Treg subpopulation of estrogen deficiency induced bone loss mice].

OBJECTIVE: To observe the effect of Modified Zuoguiwan (MZ) on the balance between helper T cell subsets 17 (Th17) and regulatory T cell subsets (Treg) in estrogen deficiency induced bone loss mice and to explore its mechanism. METHODS: Totally 50 BALB/c mice were divided into the sham-operation group, the ovariectomy model group, the low dose MZ group, the middle dose MZ group, and the high dose MZ group by random digit table, 10 in each group. Mice in the low, middle, and high dose MZ groups were respectively administered with MZ at the daily dose of 7.25, 14.50, and 29.00 g/kg by gastrogavage, 0.5 mL each time for 12 successive weeks. Meanwhile, mice in the sham-operation group and the ovariectomy model group were administered with equal volume by gastrogavage, 0.50 mL each time. The serum estradiol (E2) level was assessed by enzyme linked immunosorbent assay (ELISA). Bone mineral density (BMD) of thigh bone was measured with dual energy X ray absorptiometry. In addition, the population of Th17/Treg subsets in spleen mononuclear cells was analyzed by extracellular and intracellular staining method using flow cytometry. Moreover, the mRNA expression of IL-17A and TGF-ß in the spleen mononuclear cells was detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Compared with the sham-operation group, both E2 and BMD significantly decreased, the percentage of Th17 subset and Th17/Treg ratio both increased, the percentage of Treg subset obviously decreased, the expression of IL-17A mRNA significantly increased, and the expression of TGF-ß mRNA significantly decreased in the ovariectomy model group (all P < 0.05). Compared with the model group, BMD obviously increased, the percentage of Th17 subset and Th17/Treg ratio both decreased, the percentage of Treg subset obviously increased, the expression of IL-17A mRNA significantly decreased, and the expression of TGF-ß mRNA significantly increased in the middle dose MZ group and the high dose MZ group (all P < 0. 05). Correlation analyses showed that BMD was positively related to both the serum E2 level and the percentage of Treg subset (P < 0.05), but negatively related to the percentage of Th17 subset (P < 0.05). In addition, the serum E2 level was positively related to the percentage of Treg subset, but obviously negatively related to that of Th17 subset (P < 0.05). CONCLUSIONS: There was correlation between Th17/Treg imbalance and E2 deficient bone loss. MZ could decrease the proportion of Th17 subset, but elevate the proportion of Treg subset in E2 deficient bone loss mice. It could achieve therapeutic effect through adjusting the balance of Th17/Treg in E2 deficient bone loss mice.