Vulvovaginal candidosis (VVC) is one of the most common infectious diseases of the female reproductive tract. Approximately 75% of women experience at least one episode of VVC during their reproductive years, 1 while 40%-50% experience it twice, and nearly 5% of adult women are affected intractably and recurrently. Eighty-five to 95% of all VVC cases are caused by the commensal yeast Candida albicans. 2 In recent years, multiple in vitro and in vivo studies have demonstrated that higher levels of oestrogen affect C. albicans colonisation and increase the likelihood of women developing VVC. [3][4][5][6] In light of the emerging links between oestrogen and VVC, it is important to consider whether such effects are exerted directly on the fungal cells, or on the host, or both. | V VC IN D IFFERENT G ROUPS OF WO MENPhysiologically speaking, the level of sex hormones, mainly oestrogen and progesterone, in women of childbearing age has a cyclical pattern. In the early menstrual (ovarian) cycle, oestrogen production

Aluminium hydroxide (alum), the most widely used adjuvant in human and animal vaccines, has long been known to promote T helper type 2 (Th2) responses and Th2-associated humoral responses, but the mechanisms have remained poorly understood. In this study, we explored whether alum is able to directly modulate antigen-presenting cells to enhance their potency for Th2 polarization. We found that alum treatment of dendritic cells failed to show any Th2-promoting activities. In contrast, alum was able to enhance the capacity of basophils to induce Th2 cells. When basophils from interleukin-4 (IL-4) knockout mice were examined, the intrinsic Th2-promoting activities by basophils were largely abrogated, but the alum-enhanced Th2-promoting activities on basophils were still detectable. More importantly, Th2-promoting adjuvant activities by alum found in IL-4 knockout mice were also largely reduced when basophils were depleted by antibody administration. Therefore, basophils can mediate Th2-promoting activities by alum both in vitro and in vivo through IL-4-independent mechanisms. Further studies revealed that secreted soluble molecules from alum-treated basophils were able to confer the Th2-promoting activities, and neutralization of thymic stromal lymphopoietin or IL-25 attenuated the IL-4-independent development of Th2 cells elicited by alum-treated basophils. Finally, alum was able to activate NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in murine basophils in the same way as alum in professional antigen-presenting cells, but NLRP3 was not required for Th2-promoting activities on basophils by alum in vitro. These results demonstrated that alum can enhance the capacities of basophils to polarize Th2 cells via IL-4- and NLRP3-independent pathways.

Functioned as α-subunit of the high-affinity immunoglobulin E receptor (FcϵRIα), FcϵRIα plays a central role in the pathogenesis of Ig-E-mediated allergy and other IgE-related disorders. FcϵRIα is normally expressed only in limited spectrum of cells like basophils and mast cells, but the mechanism of controlling FcϵRIα expression in these cells is less well understood. In this study, we found fully overlapped natural antisense transcript (NATs) of FcϵRIα (FCER1A-AS) is co-expressed with cognate sense transcript (FCER1A-S) in IL-3 induced FcϵRIα-expressing cells or in high FcϵRIα-expressing cell line MC/9. When FCER1A-AS is selectively knocked down by CRISPR/RfxCas13d (CasRx) approach in MC/9, expression of mRNA and proteins of FCER1A-S is also markedly decreased. Furthermore, deficiency of FCER1A-AS along with lack of FCER1A-S expression is found in two different lines of gene-targeted mice in which FCER1A locus is disturbed at different sites. More importantly, the FCER1A-AS-deficient homozygous mice display similarly diminished anaphylactic reaction as FCER1A gene knockout mice. Thus, we uncovered in this investigation that the expression of FCER1A-S is positively regulated by co-expressed fully overlapped antisense transcript.

FcεRIα is responsible for high-affinity binding with the Fc portion of IgE, which is critical for IgE-dependent disease responses such as allergy responses and anti-parasite immunity. FcεRIα is expressed on a few cell types, including mast cells and basophils.