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Dendritic cells (DCs) that express T cell immunoglobulin domain molecule-4 (TIM4), a cell surface receptor for phosphatidylserine, induce T helper 2 (TH2) cell responses and allergic reactions. We elucidated the role of the transcription factor X-box–binding protein-1 (XBP1) in the induction of the TH2 cell response through its role in generating TIM4+ DCs. We found that XBP1 was required for TIM4 mRNA and protein expression in airway DCs in response to the cytokine interleukin-2 (IL-2) and that this pathway was required for TIM4 expression on DCs in response to the allergens PM2.5 and Derf1. The IL-2–XBP1–TIM4 axis in DCs contributed to Derf1/PM2.5-induced, aberrant TH2 cell responses in vivo. An interaction between the guanine nucleotide exchange factor Son of sevenless-1 (SOS1) and the GTPase RAS promoted XBP1 and TIM4 production in DCs. Targeting the XBP1-TIM4 pathway in DCs prevented or alleviated experimental airway allergy. Together, these data suggest that XBP1 is required for TH2 cell responses by inducing the development of TIM4+ DCs, which depends on the IL-2–XBP1–SOS1 axis. This signaling pathway provides potential therapeutic targets for the treatment of TH2 cell–dependent inflammation or allergic diseases. Editor's summary: T helper 2 (TH2) cells mediate allergic responses, and their development depends on dendritic cells (DCs) expressing the receptor TIM4. Yang et al. found that the transcription factor XBP1 induced expression of the gene encoding TIM4 in DCs. Production of the cytokine IL-2 in the airways of allergen-exposed mice induced expression of XBP1 and then TIM4 in DCs through a pathway involving the GEF Sos1 and the GTPase Ras. Targeting this pathway in DCs reduced the severity of experimentally induced allergic airway responses in mice, suggesting that these factors could be therapeutic targets for treating TH2 cell–dependent inflammatory or allergic diseases. —John F. Foley [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a disease that frequently relapses and affects more than 0.1% general population; the underlying mechanism is poorly understood. Published data show that polymorphonuclear neutrophils (PMN) contribute to the pathogenesis of UC. This study aims to identify antigen (Ag)‐specific PMNs and investigate their role in UC relapse. In this study, the correlation between PMN activities and UC relapse was assessed in a group of UC patients. A UC mouse model was developed to expand the findings of UC patient study. The results showed that a positive correlation was detected between the high PMN activities and the food Ag‐specific IgG amounts in colon biopsies of UC patients. UC patient‐derived Ag‐specific PMNs could be activated upon exposure to food specific Ag. The Ag/FcγRI complexes were detected on the surface of PMNs in UC patients. Re‐exposure of sensitized PMNs to specific Ag triggered PMN activation and induced UC‐like inflammation in the mouse colon. We conclude that FcγRI plays a critical role in UC relapse. Inhibition of FcγRI can efficiently inhibits experimental UC. [ABSTRACT FROM AUTHOR]

Background: The eosinophil (Eo) activation is a crucial factor evoking allergic rhinitis (AR) attacks; factors; the mechanism of triggering Eo activation remains to be further investigated. The interaction of antigen (Ag) and antibody plays a critical role in evoking allergy attacks. This study aims to elucidate the role of FcγRI, the high affinity receptor of IgG, in the Ag-mediated Eo activation. Methods: Nasal lavage fluids (NLF) were collected from AR patients and healthy control (HC) subjects. Eos were isolated by flow cytometry cell sorting and analyzed by pertinent immunological approaches. Results: Eos composed more than 60% of the cellular components in AR NLF. Exposure to specific Ags (sAgs) in the culture triggered Eos to release inflammatory mediators. High levels of FcγRI were detected on the surface of AR NLF Eos. Exposure to lipopolysaccharide markedly increased the FcγRI expression in naive Eos, which could be bound by Ag-specific IgG (sIgG) to form complexes on the surface of Eos; this made Eos at the sensitized status. Eos bore with the sIgG/FcγRI complexes could be activated upon exposure to sIgG in the culture; these Eos can be designated as Ag-specific Eos. Passive transfer of Ag-specific Eos resulted in profound AR response in mice upon sAg challenge. Depletion of FcγRI on Eos efficiently abolished AR response in mice. Conclusions: AR Eos express high levels FcγRI, that can be bound by sIgG to make Eos sensitized. Re-exposure to specific Ags can activate the sensitized Eos. [ABSTRACT FROM AUTHOR]

Background: The on‐purpose‐modulated dendritic cells (DCs) have shown charming effects on restoring immune regulatory functions in subjects with immune diseases. Objective: This study aims to construct DCs carrying chimerical antigen (Ag) peptides (CAP‐DCs) to induce interleukin (IL)‐17+ inducible Tregs (iTregs) to alleviate food allergy (FA) in a murine model. Methods: In this study, we constructed CAP‐DCs. The CAP is a fusion protein, consisting of a segment of recombinant scFv of anti‐DEC205 antibody and an ovalbumin (OVA) epitope (IC). A murine OVA‐FA model was developed to test the effects of CAP‐DCs on suppressing the allergic response in the intestine. Results: The CAP‐DCs are characterized as that a complex of scFv‐IC is presented on the surface of the cells, moderately express CD80 and CD86 as well as IL‐6, IL‐23, transforming growth factor (TGF)‐β and CCR9. After being passively transferred with CAP‐DCs or injection of scFv‐IC, Ag‐specific IL‐17+ Foxp3+ iTregs were induced in the intestinal lamina propria of FA mice. The iTregs showed immune suppressive effects on Ag‐specific Th2 response. FA mice were adoptively transferred with the CAP‐DCs or scFv‐IC injection, which resulted in a significant decrease in the number of Ag‐specific Th2 cells and suppression of FA response in an Ag‐specific manner. Conclusions and Clinical Relevance: CAP‐DCs can ameliorate FA response by inducing Ag‐specific IL‐17+ Foxp3+ iTregs and suppressing Ag‐specific Th2 response. To generate CAP‐DCs has the translational potential in the treatment of FA. [ABSTRACT FROM AUTHOR]

T helper (Th)2 polarization plays an important role in the pathogenesis of allergic diseases; the underlying mechanism remains to be further investigated. B cell lymphoma protein‐2 like protein‐12 (Bcl2L12) has the anti‐apoptotic function. This study aims to elucidate the contribution of Bcl2L12 to Th2 polarization in patients with allergic rhinitis (AR). In this study, human CD4+ T cells were isolated from blood samples collected from AR patients and healthy control (HC) subjects. The immune response profiles of CD4+ T cells were analyzed by immunologic approaches. The results showed that AR CD4+ T cells (CD4+ T cells collected from AR patients) showed defects of apoptosis. The expression of FasL in AR CD4+ T cells was lower than that of HC CD4+ T cells. Serum IL‐5 levels were negatively correlated with the expression of FasL in AR CD4+ T cells. Exposure of CD4+ T cells to IL‐5 in the culture suppressed the expression of FasL and increased the expression of Bcl2L12. IL‐5 increased the levels of Bcl2L12 in CD4+ T cells, the latter bound to the FasL promoter to prevent FasL gene transcription. Inhibition of Bcl2L12 restored the apoptosis machinery in AR CD4+ T cells. In conclusion, overexpression of Bcl2L12 in CD4+ T cells compromises the apoptosis machinery; the latter can be restored by inhibition of Bcl2L12. BcL2L12 in CD4+ T cells may be a novel target for the treatment of AR and other allergic disorders. CD4+ T cells express Bcl2L12, which restricts FasL expression and induces apoptotic defects in CD4+ T cells. [ABSTRACT FROM AUTHOR]

The article offers a study of 3‐methyl‐4‐nitrophenol (MNP), one of the components of diesel‐exhaust particles which l facilitates development of intestinal allergy Topics include exposure of mice fed with MNP and OVA daily showing that exposure to MNP increased absorption of FITC‐ dextran and induced intestinal epithelial barrier dysfunction and facilitated the development of intestinal allergy and suggests that environmental pollution may contribute to the development of allergic disease.