Follicular helper T cells mediate IgE antibody response to airborne allergens

BACKGROUND: TH2 cells have long been believed to play a pivotal role in allergic immune responses, including IgE antibody production and type 2 cytokine-mediated inflammation and pathology. A new T-cell subset, follicular helper T (TFH) cells, is specialized in supporting B-cell maturation and antibody production. OBJECTIVE: We sought to investigate the roles of TFH cells in allergic immune responses. METHODS: Naive mice were exposed to cytokines or natural allergens through the airways. Development of allergic immune responses was analyzed by collecting draining lymph nodes and sera and by challenging the animals. Cytokine reporter mice and gene-deficient mice were used to dissect the immunologic mechanisms. RESULTS: We observed the development of IL-4-producing TFH cells and TH2 cells in draining lymph nodes after airway exposure to IL-1 family cytokines or natural allergens. TFH and TH2 cells demonstrated unique phenotypes, tissue localization, and cytokine responses. TFH cells supported the sustained production of IgE antibody in vivo in the absence of other T-cell subsets or even when TH2 cell functions were severely compromised. Conversely, conditional deficiency of the master regulator Bcl6 in CD4+ T cells resulted in a marked reduction in TFH cell numbers and IgE antibody levels, but type 2 cytokine responses and eosinophilic inflammation in the airways remained unaffected. CONCLUSION: TFH cells play critical roles in the regulation of IgE antibody production. Allergic immune responses to airborne allergens likely involve 2 distinct subsets of IL-4-producing CD4+ T cells, namely TFH and Th2 cells

Application of TensorFlow to recognition of visualized results of fragment molecular orbital (FMO) calculations

We have applied Google's TensorFlow deep learning toolkit to recognize the visualized results of the fragment molecular orbital (FMO) calculations. Typical protein structures of alpha-helix and beta-sheet provide some characteristic patterns in the two-dimensional map of inter-fragment interaction energy termed as IFIE-map (Kurisaki et al., Biophys. Chem. 130 (2007) 1). A thousand of IFIE-map images with labels depending on the existences of alpha-helix and beta-sheet were prepared by employing 18 proteins and 3 non-protein systems and were subjected to training by TensorFlow. Finally, TensorFlow was fed with new data to test its ability to recognize the structural patterns. We found that the characteristic structures in test IFIE-map images were judged successfully. Thus the ability of pattern recognition of IFIE-map by TensorFlow was proven.Comment: 26 pages, 3 figures, 4 table

Airway exposure initiates peanut allergy by involving the IL-1 pathway and T follicular helper cells in mice

BACKGROUND: Little is currently known regarding the immunologic mechanism(s) that initiate peanut allergy. Notably, peanut proteins have been detected in house dust, and their levels correlate with peanut allergy prevalence. OBJECTIVE: This study aimed to develop a new mouse model for peanut allergy and to investigate the immunologic mechanisms involved in peanut allergen sensitization. METHODS: To mimic environmental exposure, naive mice were exposed to peanut flour by inhalation for up to 4 weeks. We then analyzed serum levels of IgE antibody and challenged mice with peanut proteins. Immunological mechanisms involved in sensitization were analyzed using cytokine reporter mice, an adoptive cell transfer model, and gene knockout mice. RESULTS: When exposed to peanut flour by inhalation, both BALB/c and C57BL/6 mice developed peanut allergy, as demonstrated by the presence of peanut-specific IgE antibodies and manifestation of acute anaphylaxis on challenge. A large number of follicular helper T (Tfh) cells were also detected in draining lymph nodes of allergic mice. These cells produced IL-4 and IL-21, and they more robustly promoted peanut-specific IgE production than Th2 cells did. Genetic depletion of Tfh cells decreased IgE antibody levels and protected mice from anaphylaxis, without affecting Th2 cells. Furthermore, peanut flour exposure increased lung levels of IL-1α and IL-1β, and mice deficient in the receptor for these cytokines showed a significant decrease in Tfh cells compared with in wild-type mice. CONCLUSIONS: Tfh cells play a key role in peanut allergy, and the IL-1 pathway is involved in the Tfh response to peanut allergen exposure

[Translation] Michael Pawlik, Das Unrecht des Bürgers(3)

監訳 : 飯島暢、川口浩一訳 : 飯島暢、中村悠人、安達光

Extended x-ray absorption fine structure study on the cerium(IV)-induced DNA hydrolysis: Implication to the roles of 4f orbitals in the catalysis

At various Ce(IV)/DPP (DPP: diphenyl phosphate) molar ratios, the structure of Ce clusters in aqueous solutions was studied by extended x-ray absorption fine structure measurements. Although the Ce–Ce bond was strong in the absence of DPP, the corresponding signal was significantly reduced when the Ce(IV)/DPP molar ratio was 1. The result indicates the existence of a strong interaction between Ce(IV) ions and DPP, and suggests the formation of a Ce–DPP structure in solution. With an increase in the molar ratio, the signal of Ce–Ce bonds increased again, and exceeded that observed in the absence of DPP, suggesting the formation of a Ce–Ce–DPP structure. Ce(IV) ions in the complexes were found to have ~ 0.67 4f electrons. On the other hand, no measurable charge transfer was observed in the case of Ce(III) ions. These results demonstrate the role of the 4f orbital of Ce(IV) ions for its enormous activity for DNA hydrolysis

血清TARC/CCL17値は薬剤性過敏症症候群(DIHS) の早期診断および病勢の指標となりうる。

BACKGROUND:Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a serious acute drug reaction with fever, cutaneous eruption, lymphadenopathy, and several visceral dysfunctions. Eosinophilia is a common hematological abnormality in DIHS/DRESS suggesting that the Th2-type immune response is involved. Thymus and activation-regulated chemokine (TARC/CCL17) is a family of CC chemokines known to play an important role in Th2-mediated immune-inflammatory processes. OBJECTIVE:We investigated the pathogenic role of TARC in patients with DIHS. METHODS:Sera were obtained from 8 patients with DIHS, 7 patients with Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN), and 14 patients with drug-induced maculopapular exanthema (MPE). Serum TARC levels were measured by ELISA. TARC levels were then compared with clinical symptoms and various hematological parameters. In addition, a biopsy was taken from the lesional skin of patients with DIHS and stained with anti-TARC Ab and anti-CD11c Ab. RESULTS:Serum TARC levels in patients with DIHS were significantly higher than those in patients with SJS/TEN and MPE during the acute phase. Serum TARC levels in DIHS patients correlated with skin eruptions, serum sIL-2R levels, eosinophil counts, and serum IL-5 levels. Immunohistochemical staining revealed that TARC was mainly expressed on CD11c+ dermal dendritic cells in patients with DIHS. CONCLUSION:Serum TARC levels may be associated with the initial presentation of DIHS as well as disease activity during the course. Thus, they could be useful as an indicator for early diagnosis and assessment of disease activity in DIHS. CD11c+ dendritic cells may be the main source of TARC in patients with DIHS.博士（医学）・甲第597号・平成25年3月15日Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved

Michael Pawlik, Das Unrecht des Bürgers(4)

監訳：飯島暢、川口浩一　訳：安達光