Junyoung Lee

Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine

Keeping immune cells quiet on a diet Over thousands of years, our immune systems has evolved to distinguish self from foreign, perpetrating attacks on microbes but not ourselves. Given this, why do we fail to mount an immune response against most of the food we eat? Kim et al. compared normal mice, mice lacking microbes, and mice lacking microbes that were fed an elemental diet devoid of dietary antigens (see the Perspective by Kuhn and Weiner). Dietary antigens normally induced a population of suppressive immune cells called regulatory T cells in the small intestine. The cells were distinct from regulatory T cells induced by microbial antigens and prevented strong reactions against food. Science, this issue p. 858; see also p. 810 A population of suppressive T cells in the small intestine of mice prevents immune responses to solid foods. [Also see Perspective by Kuhn and Weiner] Dietary antigens are normally rendered nonimmunogenic through a poorly understood “oral tolerance” mechanism that involves immunosuppressive regulatory T (Treg) cells, especially Treg cells induced from conventional T cells in the periphery (pTreg cells). Although orally introducing nominal protein antigens is known to induce such pTreg cells, whether a typical diet induces a population of pTreg cells under normal conditions thus far has been unknown. By using germ-free mice raised and bred on an elemental diet devoid of dietary antigens, we demonstrated that under normal conditions, the vast majority of the small intestinal pTreg cells are induced by dietary antigens from solid foods. Moreover, these pTreg cells have a limited life span, are distinguishable from microbiota-induced pTreg cells, and repress underlying strong immunity to ingested protein antigens.

Affinity for self antigen selects Treg cells with distinct functional properties

The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully understood. We identified two Treg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITRhiPD-1hiCD25hi (Triplehi) Treg cells were highly self-reactive and controlled lympho-proliferation in peripheral lymph nodes. GITRloPD-1loCD25lo (Triplelo) Treg cells were less self-reactive and limited the development of colitis by promoting the conversion of CD4+ Tconv cells into induced Treg cells (iTreg cells). Although Foxp3-deficient (Scurfy) mice lacked Treg cells, they contained Triplehi-like and Triplelo-like CD4+ T cells zsuper> T cells infiltrated the skin, whereas Scurfy TripleloCD4+ T cells induced colitis and wasting disease. These findings indicate that the affinity of the T cell antigen receptor for self antigen drives the differentiation of Treg cells into distinct subsets with non-overlapping regulatory activities.

Structural characterization of the Fddd phase in a diblock copolymer thin film by electron microtomography

A 3-dimensional Fddd network structure of a polystyrene-block-polyisoprene (PS-b-PI) diblock copolymer (Mn = 31500, fPI = 0.645) was observed for the first time in real space by transmission electron microtomography (TEMT). In a 650 nm thick film of the PS-b-PI thin film on a silicon wafer, the Fddd phase was developed after annealing at 215 °C for 24 h. The single network structure consists of the connected tripodal units of minor PS block domains. The {111}Fddd plane, the densest plane of the minor PS phase, was found to orient parallel to the film plane. The transitional structure from the wetting layer at the free surface to the internal {111}Fddd plane via a perforated layer structure was also observed.

Threshold Voltage Variations Due to Oblique Single Grain Boundary in Sub-50-nm Polysilicon Channel

We investigate the effect of single grain boundary (SGB) with arbitrary angles on the threshold voltage (Vth) variation in sub-50-nm polysilicon (poly-Si) channel devices using 3-D simulation. An SGB in the poly-Si channel causes changes in potential barrier profile resulting in the variation of Vth. As the planar devices scale down to 20-nm, oblique SGB can significantly increase the whole potential barrier profile and cause large Vth variation. However, due to superior gate controllability, the gate-all-around devices show relatively small increase of the conduction energy band, and thus mitigate the Vth variation even in 20-nm poly-Si channel.

Dendritic cell expression of the signaling molecule TRAF6 is required for immune tolerance in the lung

Direct effects of antibiotics in lung DC-mediated immune tolerance

Three-dimensional simulation of threshold voltage variations due to an oblique single grain boundary in sub-40 nm polysilicon nanowire FETs

We perform a comparative study of the threshold voltage (Vth) variation between inversion-mode and junctionless nanowire devices with oblique single grain boundary (o-SGB) in a sub-40 nm poly-silicon (Poly-Si) channel using 3D simulation. The Vth variation due to the o-SGB becomes significant as the devices scale down to 20 nm where the o-SGB can fully affect the whole channel potential. In addition, due to relatively less flat energy band in the channel, the junctionless Poly-Si nanowire devices show larger Vth variation compared with the inversion-mode devices.

The variability due to random discrete dopant and grain boundary in 3D NAND unit cell

We investigate the electrical variability of polysilicon (poly-Si) channels with the single discrete dopant (SDD) and single grain boundary (SGB) for 3D NAND applications. A 3D simulation is used to investigate the effect of the SGB and the SDD on the threshold voltage (Vth) and subthreshold swing (S/S) variation where the SDD and SGB are randomly located in poly-Si channels. The SGB affects the entire channel potential and causes the Vth and S/S variations. On the other hand, the SDD can cause only small fluctuation in the S/S characteristics.

Spontaneous Proliferation of CD4+ T Cells in RAG-Deficient Hosts Promotes Antigen-Independent but IL-2-Dependent Strong Proliferative Response of Naïve CD8+ T Cells

The fast and intense proliferative responses have been well documented for naïve T cells adoptively transferred into chronic lymphopenic hosts. This response known as spontaneous proliferation (SP), unlike antigen-independent lymphopenia-induced proliferation (LIP), is driven in a manner dependent on antigens derived from commensal microbiota. However, the precise nature of the SP response and its impact on homeostasis and function for T cells rapidly responding under this lymphopenic condition are still unclear. Here we demonstrate that, when naïve T cells were adoptively transferred into specific pathogen-free (SPF) but not germ-free (GF) RAG−/− hosts, the SP response of these cells substantially affects the intensity and tempo of the responding T cells undergoing LIP. Therefore, the resulting response of these cells in SPF RAG−/− hosts was faster and stronger than the typical LIP response observed in irradiated B6 hosts. Although the intensity and tempo of such augmented LIP in SPF RAG−/− hosts were analogous to those of antigen-dependent SP, the former was independent of antigenic stimulation but most importantly, dependent on IL-2. Similar observations were also apparent in other acute lymphopenic settings where antigen-dependent T cell activation can strongly occur and induce sufficient levels of IL-2 production. Consequently, the resulting T cells undergoing IL-2-driven strong proliferative responses showed the ability to differentiate into functional effector and memory cells that can control infectious pathogens. These findings therefore reveal previously unappreciated role of IL-2 in driving the intense form of T cell proliferative responses in chronic lymphopenic hosts.

Phenotypic and Functional Changes of Peripheral Ly6C+ T Regulatory Cells Driven by Conventional Effector T Cells

A relatively high affinity/avidity of T cell receptor (TCR) recognition for self-peptide bound to major histocompatibility complex II (self-pMHC) ligands is a distinctive feature of CD4 T regulatory (Treg) cells, including their development in the thymus and maintenance of their suppressive functions in the periphery. Despite such high self-reactivity, however, all thymic-derived peripheral Treg populations are neither homogenous in their phenotype nor uniformly immune-suppressive in their function under steady state condition. We show here that based on the previously defined heterogeneity in the phenotype of peripheral Treg populations, Ly6C expression on Treg marks a lower degree of activation, proliferation, and differentiation status as well as functional incompetence. We also demonstrate that Ly6C expression on Treg in a steady state is either up- or downregulated depending on relative amounts of tonic TCR signals derived from its contacts with self-ligands. Interestingly, peripheral appearance and maintenance of these Ly6C-expressing Treg cells largely differed in an age-dependent manner, with their proportion being continuously increased from perinatal to young adult period but then being gradually declined with age. The reduction of Ly6C+ Treg in the aged mice was not due to their augmented cell death but rather resulted from downregulation of Ly6C expression. The Ly6C downregulation was accompanied by proliferation of Ly6C+ Treg cells and subsequent change into Ly6C− effector Treg with concomitant restoration of immune-suppressive activity. Importantly, we found that this phenotypic and functional change of Ly6C+ Treg is largely driven by conventional effector T cell population. Collectively, these findings suggest a potential cross-talk between peripheral Treg subsets and effector T cells and provides better understanding for Treg homeostasis and function on maintaining self-tolerance.

Highly Enhanced Performance of Network Channel Polysilicon Thin-Film Transistors

This letter presents the electrical characteristics of newly proposed network-channel low-temperature polysilicon channel (LTPS) thin-film transistors (TFTs). Due to effective reduction of grain boundary traps and enhanced gate controllability, the network-channel TFTs show better subthreshold slope, lower threshold voltage, and higher ON- OFF current ratio, compared with conventional planar devices. The extracted grain boundary trap density and the interface trap density are significantly reduced in the network-channel devices. In addition, the network-channel devices show higher immunity to hot-carrier stressing, which are confirmed from the low-frequency noise characteristics with various stressing time. These results suggest that the network-channel devices are very promising for next-generation LTPS TFT applications.