Favorable effect of modest alcohol consumption to fatty liver disease

We previously reported that modest alcohol consumption was significantly inversely associated with fatty liver disease.Feng et al pointed out a discrepancy of statistical significance between our current larger scale cohort and a previous cohort.However,the prevalence of non-alcoholic fatty liver disease was higher in non or minimal drinkers than those in light drinkers in both cohorts.They also argue that some potential co-factors such as soft drink consumption and genetic variations should be discussed.

Multiple sclerosis:why we should focus on both sides of the(auto)antibody

Various clinical and experimental findings suggest a pathogenic role of antibodies in multiple sclerosis(MS).Yet,whether antibodies contribute to the pathogenesis or progression of MS is still a subject of intense debate.This controversy particularly results from unclarity regarding the target antigens of the antibodies that are found in the central nervous system(CNS)of MS patients.

Intravenous immunoglobulin suppresses IL-10 production by activated B cells in vitro

A therapeutic preparation of polyclonal human IgG, i.e., intravenous immunoglobulin (IVIg), has been employed to treat several inflammatory and autoimmune disorders. B cells are supposed to be a target of IVIg, but the molecular mechanism is elusive because of the lack of a suitable experimental system. To gain an insight into the beneficial effect of IVIg on B cells, we first established an experimental setting in which IVIg modulates a murine B cell function in vitro, and then aimed at identifying the mechanistic features at the molecular level. Here we show that IVIg down-regulates IL-10 production by CpG-activated B cells in vitro. The responsible component of IVIg was identified as the F(ab’)2 portion, whose polyclonality is mandatory for the suppressive effect. IVIg, bound to the surface of activated B cells, was found to be co-localized with intracellular SHP-1 on confocal laser microscopy, suggesting that B cell-surface immunoreceptor tyrosine-based inhibitory motif-harboring receptors that recruit SHP-1 are target molecules for IVIg in our experimental setting. Overall, we postulate a scenario in which IVIg attenuates B cells by suppressing IL-10 production, a B cell growth factor, and thus down-regulates the production of pathogenic antibodies.

CXCR5^(+)PD-1^(++)CD4^(+)T cells colonize infant intestines early in life and promote B cell maturation

Gastrointestinal infections are a major cause for serious clinical complications in infants.The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++CD4+T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++CD4+T cells in human intestines.While CXCR5+PD-1++CD4+T cells were absent in fetal intestines,CXCR5+PD-1++CD4+T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to adults.These findings were supported by scRNAseq analyses,showing increased frequencies of CD4+T cells with a TFH gene signature in infant intestines compared to blood.Co-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B cells.Taken together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.

Anaphylaxis and generalized urticaria from eating Chinese bayberry fruit

Chinese bayberry Myrica rubra is a very popular fruit in southeastern China.In spite of its wide consumption,no allergies to this fruit have been reported previously.Here we report on a 40-year-old woman suffering from anaphylaxis to Chinese bayberry fruit.Prick-prick skin tests revealed strong reactions to fresh Chinese bayberry fruits as well as to peach,and weaker reactions to some other fruits including apple,melon,and banana.ImmunoCAP analysis revealed identical titers of specific IgE(4.3 kU A /L) to peach extract and its lipid transfer protein(LTP,rPru p 3),which was confirmed by detection of a 9 kD band following immunoblotting.Immunoblot analysis with Chinese bayberry extract gave bands of 22,45,and 90 kD,but no 9 kD band was recognized.There was also no evidence of LTP recognition for loquat(36 kD) or melon(24 kD).This first report of a severe allergic reaction to Chinese bayberry fruit in a patient with LTP-mediated peach allergy indicates that other as yet unidentified non-pollen related fruit allergens are involved in this new severe fruit allergy.

Recirculating IL-1R2^(+) Tregs fine-tune intrathymic Treg development under inflammatory conditions

The vast majority of Foxp3^(+)regulatory T cells(Tregs)are generated in the thymus,and several factors,such as cytokines and unique thymic antigen-presenting cells,are known to contribute to the development of these thymus-derived Tregs(tTregs).Here,we report the existence of a specific subset of Foxp3^(+)Tregs within the thymus that is characterized by the expression of IL-1R2,which is a decoy receptor for the inflammatory cytokine IL-1.Detailed flow cytometric analysis of the thymocytes from Foxp3^(hCD2)xRAG1^(GFP) reporter mice revealed that the IL-1R2^(+)Tregs are mainly RAG1^(GFP-)and CCR6^(+)CCR7^(-),demonstrating that these Tregs are recirculating cells entering the thymus from the periphery and that they have an activated phenotype.In the spleen,the majority of IL-1R2^(+)Tregs express neuropilin-1(Nrp-1)and Helios,suggesting a thymic origin for these Tregs.Interestingly,among all tissues studied,the highest frequency of IL-1R2^(+)Tregs was observed in the thymus,indicating preferential recruitment of this Treg subset by the thymus.Using fetal thymic organ cultures(FTOCs),we demonstrated that increased concentrations of exogenous IL-1β blocked intrathymic Treg development resulting in a decreased frequency of CD25^(+)Foxp3^(+)tTregs and an accumulation of CD25^(+)Foxp3^(-)Treg precursors.Interestingly,the addition of IL-1R2^(+)Tregs,but not IL-1R2^(+)Tregs,to reaggregated thymic organ cultures(RTOCs)abrogated the IL-1β-mediated blockade,demonstrating that these recirculating IL-1R2^(+)Tregs can quench IL-1 signaling in the thymus and thereby maintain thymic Treg development even under inflammatory conditions.