Sensory neurons promote immune homeostasis in the lung.

Cytokines employ downstream Janus kinases (JAKs) to promote chronic inflammatory diseases. JAK1-dependent type 2 cytokines drive allergic inflammation, and patients with JAK1 gain-of-function (GoF) variants develop atopic dermatitis (AD) and asthma. To explore tissue-specific functions, we inserted a human JAK1 GoF variant (JAK1GoF) into mice and observed the development of spontaneous AD-like skin disease but unexpected resistance to lung inflammation when JAK1GoF expression was restricted to the stroma. We identified a previously unrecognized role for JAK1 in vagal sensory neurons in suppressing airway inflammation. Additionally, expression of Calcb/CGRPß was dependent on JAK1 in the vagus nerve, and CGRPß suppressed group 2 innate lymphoid cell function and allergic airway inflammation. Our findings reveal evolutionarily conserved but distinct functions of JAK1 in sensory neurons across tissues. This biology raises the possibility that therapeutic JAK inhibitors may be further optimized for tissue-specific efficacy to enhance precision medicine in the future.

Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection.

Nociceptive pain is a hallmark of many chronic inflammatory conditions including inflammatory bowel diseases (IBDs); however, whether pain-sensing neurons influence intestinal inflammation remains poorly defined. Employing chemogenetic silencing, adenoviral-mediated colon-specific silencing, and pharmacological ablation of TRPV1+ nociceptors, we observed more severe inflammation and defective tissue-protective reparative processes in a murine model of intestinal damage and inflammation. Disrupted nociception led to significant alterations in the intestinal microbiota and a transmissible dysbiosis, while mono-colonization of germ-free mice with Gram+Clostridium spp. promoted intestinal tissue protection through a nociceptor-dependent pathway. Mechanistically, disruption of nociception resulted in decreased levels of substance P, and therapeutic delivery of substance P promoted tissue-protective effects exerted by TRPV1+ nociceptors in a microbiota-dependent manner. Finally, dysregulated nociceptor gene expression was observed in intestinal biopsies from IBD patients. Collectively, these findings indicate an evolutionarily conserved functional link between nociception, the intestinal microbiota, and the restoration of intestinal homeostasis.

A basophil-neuronal axis promotes itch.

Itch is an evolutionarily conserved sensation that facilitates expulsion of pathogens and noxious stimuli from the skin. However, in organ failure, cancer, and chronic inflammatory disorders such as atopic dermatitis (AD), itch becomes chronic, intractable, and debilitating. In addition to chronic itch, patients often experience intense acute itch exacerbations. Recent discoveries have unearthed the neuroimmune circuitry of itch, leading to the development of anti-itch treatments. However, mechanisms underlying acute itch exacerbations remain overlooked. Herein, we identify that a large proportion of patients with AD harbor allergen-specific immunoglobulin E (IgE) and exhibit a propensity for acute itch flares. In mice, while allergen-provoked acute itch is mediated by the mast cell-histamine axis in steady state, AD-associated inflammation renders this pathway dispensable. Instead, a previously unrecognized basophil-leukotriene (LT) axis emerges as critical for acute itch flares. By probing fundamental itch mechanisms, our study highlights a basophil-neuronal circuit that may underlie a variety of neuroimmune processes.

TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells.

Intestinal macrophages are critical for gastrointestinal (GI) homeostasis, but our understanding of their role in regulating intestinal motility is incomplete. Here, we report that CX3C chemokine receptor 1-expressing muscularis macrophages (MMs) were required to maintain normal GI motility. MMs expressed the transient receptor potential vanilloid 4 (TRPV4) channel, which senses thermal, mechanical, and chemical cues. Selective pharmacologic inhibition of TRPV4 or conditional deletion of TRPV4 from macrophages decreased intestinal motility and was sufficient to reverse the GI hypermotility that is associated with chemotherapy treatment. Mechanistically, stimulation of MMs via TRPV4 promoted the release of prostaglandin E2 and elicited colon contraction in a paracrine manner via prostaglandin E receptor signaling in intestinal smooth muscle cells without input from the enteric nervous system. Collectively, our data identify TRPV4-expressing MMs as an essential component required for maintaining normal GI motility and provide potential drug targets for GI motility disorders.

ß-Ga2O3nanotube arrays for high-performance self-powered ultraviolet photoelectrochemical photodetectors.

Self-powered ultraviolet (UV) photodetectors (PDs) are critical for future energy-efficient optoelectronic systems due to their low energy consumption and high sensitivity. In this paper, the vertically alignedß-Ga2O3nanotube arrays (NTs) have been prepared on GaN/sapphire substrate by the thermal oxidation process combined with the dry etching technology, and applied in the UV photoelectrochemical photodetectors (PEC-PDs) for the first time. Based on the large specific surface area ofß-Ga2O3NTs on GaN/sapphire substrates and the solid/liquid heterojunction, the PEC-PDs exhibit excellent self-powered characteristics under 255 nm (UVA) and 365 nm (UVC) light illumination. Under 255 nm (365 nm) light illumination, the maximum responsivity of 49.9 mA W-1(32.04 mA W-1) and a high detectivity of 1.58 × 1011Jones (1.01 × 1011Jones) were achieved for theß-Ga2O3NTs photodetectors at 0 V bias. In addition, the device shows a fast rise/decay time of 8/4 ms (4/2 ms), which is superior to the level of the previously reported self-powered UV PEC-PDs. This high-performance PEC-PD has potential applications in next-generation low-energy UV detection systems.

High Power Figure-of-Merit, 10.6-kV AlGaN/GaN Lateral Schottky Barrier Diode with Single Channel and Sub-100-µm Anode-to-Cathode Spacing.

GaN-based lateral Schottky barrier diodes (SBDs) have attracted great attention for high-power applications due to its combined high electron mobility and large critical breakdown field. However, the breakdown voltage (BV) of the SBDs are far from exploiting the material advantages of GaN at present, limiting the desire to use GaN for ultra-high voltage (UHV) applications. Then, a golden question is whether the excellent properties of GaN-based materials can be practically used in the UHV field? Here, UHV AlGaN/GaN SBDs are demonstrated on sapphire with a BV of 10.6 kV, a specific on-resistance (RON,SP ) of 25.8 mΩ cm2 , yielding a power figure-of-merit (P-FOM = BV2 /RON,SP ) of 4.35 GW cm-2 . These devices are designed with single channel and 85-µm anode-to-cathode spacing, without other additional electric field management, demonstrating its great potential for the UHV application in power electronics.

Study on the controlled release and synergistic anti-oxidant activity in vitro and ex vivo of ligustrazine hydrochloride encapsulated into liposomes.

Ligustrazine with good antioxidant activity is one of the main active components of chuanxiong. We designed ligustrazine hydrochloride-loaded liposomes (LTH-L) by the thin film dispersion method. The particle size and zeta potential of liposomes was 118±10.61nm and -39.3±3.7mV, entrapment efficiency (EE%) was 75.05±10.67%. In vitro permeation across the dialysis membrane, the release rate (R%) of ligustrazine hydrochloride (LTH) and LTH-L were reached 80% and 60%. Ex Vivo transdermal behavior experiment showed the R% of LTH and LTH-L were between 30%-40%, the R% of LTH-L was slightly lower, because liposomes played the role on the sustained and controlled release of LTH. In addition, LTH, LTH-L and BL reacted with 2,2-diphenyl-1-picrylhydrazyl (DPPH) solution for two hours, the scavenge rates (SR%) were 55.06±2.73%, 11.3±0.03% and 37.25±1.12% respectively (P<0.001) and the SR% of LTH, LTH-L and BL reacted with H2O2 were 4.13±0.02%, 0.52±0.01% and 75.15±6.10%. The inhibit rate (IR%) of LTH, LTH-L and BL on malondialdehyde (MDA) in liver homogenate were 35.44±1.79%, 1.22±0.01% and 17.92±0.29% (P<0.001), the IR% were 30.82±0.93%, 1.7±0.01% and 25.19±0.60% (P<0.001) in anti-low density lipoprotein (LDL) oxidation experiments, perhaps LTH prepared into LTH-L can play a better antioxidant role.

Mechanosensitive TRPV4 is required for crystal-induced inflammation.

Crystal structures activate innate immune cells, especially macrophages and initiate inflammatory responses. We aimed to understand the role of the mechanosensitive TRPV4 channel in crystal-induced inflammation. Real-time RT-PCR, RNAscope in situ hybridisation, and Trpv4eGFP mice were used to examine TRPV4 expression and whole-cell patch-clamp recording and live-cell Ca2+ imaging were used to study TRPV4 function in mouse synovial macrophages and human peripheral blood mononuclear cells (PBMCs). Both genetic deletion and pharmacological inhibition approaches were used to investigate the role of TRPV4 in NLRP3 inflammasome activation induced by diverse crystals in vitro and in mouse models of crystal-induced pain and inflammation in vivo. TRPV4 was functionally expressed by synovial macrophages and human PBMCs and TRPV4 expression was upregulated by stimulation with monosodium urate (MSU) crystals and in human PBMCs from patients with acute gout flares. MSU crystal-induced gouty arthritis were significantly reduced by either genetic ablation or pharmacological inhibition of TRPV4 function. Mechanistically, TRPV4 mediated the activation of NLRP3 inflammasome by diverse crystalline materials but not non-crystalline NLRP3 inflammasome activators, driving the production of inflammatory cytokine interleukin-1ß which elicited TRPV4-dependent inflammatory responses in vivo. Moreover, chemical ablation of the TRPV1-expressing nociceptors significantly attenuated the MSU crystal-induced gouty arthritis. In conclusion, TRPV4 is a common mediator of inflammatory responses induced by diverse crystals through NLRP3 inflammasome activation in macrophages. TRPV4-expressing resident macrophages are critically involved in MSU crystal-induced gouty arthritis. A neuroimmune interaction between the TRPV1-expressing nociceptors and the TRPV4-expressing synovial macrophages contributes to the generation of acute gout flares.

Implantation energy- and size-dependent light output of enhanced-efficiency micro-LED arrays fabricated by ion implantation.

A new process is presented for fabricating enhanced-efficiency micro-pixelated vertical-structured light-emitting diode (µVLED) arrays based on ion-implantation technology. High-resistivity selective regions are locally introduced in the n-GaN layer by ion implantation and then used as effective and non-destructive electrical isolation for realizing µVLED arrays with ultra-small pixel diameters. The implantation energy-dependent and size-dependent opto-electrical characteristics of fluorine (F-) implanted µVLED arrays are investigated systematically. The results show that the optimally designed F- ion implantation not only can achieve smaller reverse leakage current but also can realize ion-induced thermal relaxation effectively and is more suited for fabricating high-resolution µVLED arrays with higher optical output power. For the F--implanted µVLED array with pixel diameters of 10 µm, a measured output power density reaches a value of 82.1 W cm-2 at a high injection current density of 220 A cm-2, before power saturation. Further, the output power densities and external quantum efficiencies of F--implanted µVLED arrays with pixel diameters less than 10µm show strong dependences on pixel size due to the presence of defects-related SRH process. So, the high-efficiency µVLED arrays with ultra-small pixel sizes could be fabricated by an appropriately designed ion implantation combined with control of defect densities to meet the industrial requirement of microdisplay applications.

Methotrexate, a small molecular scaffold targeting Kv1.3 channel extracellular pore region.

Methotrexate (MTX) has been widely used for the treatment of many types of autoimmune diseases, such as rheumatoid arthritis, psoriasis and dermatomyositis. However, its pharmacological mechanism is still unclear completely. In this study, we found that MTX is a potent and selective inhibitor of the Kv1.3 channel, a class of potassium channels highly associated with autoimmune diseases. Electrophysiological experiments showed that MTX inhibited human Kv1.3 channel with an IC50 of 41.5 ± 24.9 nM, and 1 µM MTX inhibited 32.6 ± 1.3% and 25.6 ± 2.2% of human Kv1.1 and Kv1.2 channel currents, respectively. These data implied the unique selectivity of MTX towards the Kv1.3 channel. Excitingly, using channel activation and chimeric experiments, we found that MTX bound to the outer pore region of Kv1.3 channel. Mutagenesis experiments in the Kv.3 channel extracellular pore region further showed that the Dsp371, Thr373 and His399 residues of outer pore region of Kv1.3 channel played important roles in MTX inhibiting activities. In conclusion, MTX inhibited Kv1.3 channel by targeting extracellular pore region, which is different form all the report small molecules, such as PAP-1 and 4-AP, but similar with many natural animal toxin peptides, such as ChTX, ShK and BmKTX. To the best of our knowledge, MTX is the first small molecular scaffold targeting the Kv1.3 channel extracellular pore region, suggesting its potential applications for designing novel Kv1.3 lead drugs and treating Kv1.3 channel-associated autoimmune diseases.

Electron-Beam-Driven III-Nitride Plasmonic Nanolasers in the Deep-UV and Visible Region.

Plasmonic nanolasers based on wide bandgap semiconductors are presently attracting immense research interests due to the breaking in light diffraction limit and subwavelength mode operation with fast dynamics. However, these plasmonic nanolasers have so far been mostly realized in the visible light ranges, or most are still under optical excitation pumping. In this work, III-nitride-based plasmonic nanolasers emitting from the green to the deep-ultraviolet (UV) region by energetic electron beam injection are reported, and a threshold as low as 8 kW cm-2 is achieved. A fast decay time as short as 123 ps is collected, indicating a strong coupling between excitons and surface plasmon. Both the spatial and temporal coherences are observed, which provide a solid evidence for exciton-plasmon coupled polariton lasing. Consequently, the achievements in III-nitride-based plasmonic nanolaser devices represent a significant step toward practical applications for biological technology, computing systems, and on-chip optical communication.

The influence of an AlN seeding layer on nucleation of self-assembled GaN nanowires on silicon substrates.

Gallium nitride (GaN)-based nanowires (NWs) have attracted much attention for the fabrication of novel nanostructured devices. In this paper, the influence of an AlN seeding layer on the nucleation of self-assembled GaN NWs grown by plasma-assisted molecular beam epitaxy (MBE) on Si (111) substrates has been investigated. Not only is the formation of a two-dimensional compact GaN layer at the bottom of the NWs suppressed, but also a high density of vertically aligned well-separated GaN NWs originating from GaN islands are successfully obtained after introducing annealing and nitridation processes. Scanning electronic microscope and transmission electron microscope measurements show that the NWs have a high crystalline wurtzite structure nearly free of dislocations and stacking faults and the NW diameter remains constant over almost the entire length. Due to the temperature-dependent diffusion length of Ga adatoms during the nucleation process, the formation of well-separated NWs relies on the distribution and morphology of the underlying AlN seeding layer. Moreover, the SiNx layer served as mask to inhibit coalescence at the nucleation sites. The developed growth processes and the obtained results provide a viable path facilitating the use of MBE growth techniques to fabricate III-nitride NW-based materials and related devices on Si substrates.

Study on the self-absorption of InGaN quantum wells at high photon density.

In this paper, the self-absorption of InGaN quantum wells at high photon density is studied based on a rectangular ridge structure. The ridge structure was fabricated based on a standard GaN-based blue LED wafer grown on (0001) patterned sapphire substrate. The high-density photons were obtained by a high-power femtosecond laser with high excitation of 42kW/cm2 at room temperature. Based on the analysis of the photoluminescence intensities of the InGaN quantum wells, we found that the absorption coefficient of the InGaN quantum wells varies with the background photon density. The results revealed that the final absorption coefficient of the InGaN quantum well decreases with the increase of photon density, which can be 48.7% lower than its normal value under our experimental conditions.

Scorpion Potassium Channel-blocking Defensin Highlights a Functional Link with Neurotoxin.

The structural similarity between defensins and scorpion neurotoxins suggests that they might have evolved from a common ancestor. However, there is no direct experimental evidence demonstrating a functional link between scorpion neurotoxins and defensins. The scorpion defensin BmKDfsin4 from Mesobuthus martensiiKarsch contains 37 amino acid residues and a conserved cystine-stabilized α/ß structural fold. The recombinant BmKDfsin4, a classical defensin, has been found to have inhibitory activity against Gram-positive bacteria such as Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteusas well as methicillin-resistant Staphylococcus aureus Interestingly, electrophysiological experiments showed that BmKDfsin4,like scorpion potassium channel neurotoxins, could effectively inhibit Kv1.1, Kv1.2, and Kv1.3 channel currents, and its IC50value for the Kv1.3 channel was 510.2 nm Similar to the structure-function relationships of classical scorpion potassium channel-blocking toxins, basic residues (Lys-13 and Arg-19) of BmKDfsin4 play critical roles in peptide-Kv1.3 channel interactions. Furthermore, mutagenesis and electrophysiological experiments demonstrated that the channel extracellular pore region is the binding site of BmKDfsin4, indicating that BmKDfsin4 adopts the same mechanism for blocking potassium channel currents as classical scorpion toxins. Taken together, our work identifies scorpion BmKDfsin4 as the first invertebrate defensin to block potassium channels. These findings not only demonstrate that defensins from invertebrate animals are a novel type of potassium channel blockers but also provide evidence of a functional link between defensins and neurotoxins.

Fabrication of AlGaN nanorods with different Al compositions for emission enhancement in UV range.

Highly ordered AlxGa1-xN nanorods with varied aluminum alloy compositions (0.18 ≤ x ≤ 0.8) are fabricated with nanoimprint lithography and top-down dry etching techniques. And the structural properties and morphology are obtained by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Compared with as-grown AlGaN samples, nanorod samples reveal outstanding optical performance on account of strain releasing and light extraction enhancement. Through Raman scattering and cathodeluminescence measurements, it has been observed clear red-shifts of E2h modes and near band edge emission (NBE) peaks of AlGaN nanorods compared to the planar ones, indicating the residual strain releasing after nano-fabrication. The integrated intensities of NBE peaks of AlGaN nanorods manifest light emission enhancement up to 2.7 at deep-UV range. Finite-difference time-domain (FDTD) simulations have been adopted to investigate the light extraction and far-field distribution of such structures, it turned out that ordered nanorod array can enhance the TM polarized emission extraction 2-7 folds compared to the planar structure. The optical regulation in nanorod arrays should take the responsibility for the observed optical enhancements, which is proved by the far-field distribution of light, thus it can improve the performance of ultraviolet LEDs.

Molecular basis for the toxin insensitivity of scorpion voltage-gated potassium channel MmKv1.

Scorpions are insensitive to their own venoms, which contain various neurotoxins specific for mammalian or insect ion channels, whose molecular mechanism remains unsolved. Using MmKv1, a potassium channel identified from the genome of the scorpion Mesobuthus martensii, channel kinetic experiments showed that MmKv1 was a classical voltage-gated potassium channel with a voltage-dependent fast activation and slow inactivation. Compared with the human Kv1.3 channel (hKv1.3), the MmKv1 channel exhibited a remarkable insensitivity to both scorpion venom and toxin. The chimaeric channels of MmKv1 and hKv1.3 revealed that both turret and filter regions of the MmKv1 channel were critical for the toxin insensitivity of MmKv1. Furthermore, mutagenesis of the chimaeric channel indicated that two basic residues (Arg(399) and Lys(403)) in the MmKv1 turret region and Arg(425) in the MmKv1 filter region significantly affected its toxin insensitivity. Moreover, when these three basic residues of MmKv1 were simultaneously substituted with the corresponding residues from hKv1.3, the MmKv1-R399T/K403S/R425H mutant channels exhibited similar sensitivity to both scorpion venom and toxin to hKv1.3, which revealed the determining role of these three basic residues in the toxin insensitivity of the MmKv1 channel. More strikingly, a similar triad sequence structure is present in all Shaker-like channels from venomous invertebrates, which suggested a possible convergent functional evolution of these channels to enable them to resist their own venoms. Together, these findings first illustrate the mechanism by which scorpions are insensitive to their own venoms at the ion channel receptor level and enrich our knowledge of the insensitivity of scorpions and other venomous animals to their own venoms.

Kv Channel S1-S2 Linker Working as a Binding Site of Human ß-Defensin 2 for Channel Activation Modulation.

Among the three extracellular domains of the tetrameric voltage-gated K(+) (Kv) channels consisting of six membrane-spanning helical segments named S1-S6, the functional role of the S1-S2 linker still remains unclear because of the lack of a peptide ligand. In this study, the Kv1.3 channel S1-S2 linker was reported as a novel receptor site for human ß-defensin 2 (hBD2). hBD2 shifts the conductance-voltage relationship curve of the human Kv1.3 channel in a positive direction by nearly 10.5 mV and increases the activation time constant for the channel. Unlike classical gating modifiers of toxin peptides from animal venoms, which generally bind to the Kv channel S3-S4 linker, hBD2 only targets residues in both the N and C termini of the S1-S2 linker to influence channel gating and inhibit channel currents. The increment and decrement of the basic residue number in a positively charged S4 sensor of Kv1.3 channel yields conductance-voltage relationship curves in the positive direction by ∼31.2 mV and 2-4 mV, which suggests that positively charged hBD2 is anchored in the channel S1-S2 linker and is modulating channel activation through electrostatic repulsion with an adjacent S4 helix. Together, these findings reveal a novel peptide ligand that binds with the Kv channel S1-S2 linker to modulate channel activation. These findings also highlight the functional importance of the Kv channel S1-S2 linker in ligand recognition and modification of channel activation.

Human α-defensins are immune-related Kv1.3 channel inhibitors: new support for their roles in adaptive immunity.

Defensins form a major family of antimicrobial peptides. Recently, human ß-defensin 2 and fungal plectasin were shown to be immune-related potassium voltage-gated channel subfamily A member 3 (Kv1.3) channel inhibitors. This work continued to show that the human α-defensins human neutrophil peptide (HNP) 1 and human defensin (HD) 5 are selective Kv1.3 channel inhibitors with 50% inhibition concentration values of 102.0 ± 30.3 nM and 2.2 ± 0.2 µM, respectively. Furthermore, HNP1 was found to inhibit Kv1.3 currents and IL-2 secretion in human CD3(+) T cells. Despite the structural similarity between HNP1 and HD5, HNP1 could simultaneously bind to the S1-S2 linker and the pore region of the Kv1.3 channel as both a toxinlike blocker and a novel modifier, whereas HD5 could only bind to the channel pore region as a toxinlike blocker. As a channel modifier, HNP1 could shift the conductance-voltage relationship curve of the Kv1.3 channel by ∼9.5 mV in the positive direction and could increase the time constant for channel activation through the electrostatic repulsion between the cationic HNP1 anchored in the S1-S2 linker and the positively charged S4 domain of the Kv1.3 channel. Together, these findings reveal that human α-defensins are novel endogenous inhibitors of Kv1.3 channels with distinct interaction mechanisms, which facilitates future research into their adaptive immune functions.

Great enhancement in the excitonic recombination and light extraction of highly ordered InGaN/GaN elliptic nanorod arrays on a wafer scale.

A series of highly ordered c-plane InGaN/GaN elliptic nanorod (NR) arrays were fabricated by our developed soft UV-curing nanoimprint lithography on a wafer. The photoluminescence (PL) integral intensities of NR samples show a remarkable enhancement by a factor of up to two orders of magnitude compared with their corresponding as-grown samples at room temperature. The radiative recombination in NR samples is found to be greatly enhanced due to not only the suppressed non-radiative recombination but also the strain relaxation and optical waveguide effects. It is demonstrated that elliptic NR arrays improve the light extraction greatly and have polarized emission, both of which possibly result from the broken structure symmetry. Green NR light-emitting diodes have been finally realized, with good current-voltage performance and uniform luminescence.

Endogenous animal toxin-like human ß-defensin 2 inhibits own K(+) channels through interaction with channel extracellular pore region.

Human potassium channels are widely inhibited by peptide toxins from venomous animals. However, no human endogenous peptide inhibitor has been discovered so far. In this study, we demonstrate for the first time using electrophysiological techniques, that endogenous human ß-defensin 2 (hBD2) is able to selectively and dose-dependently inhibit the human voltage-gated Kv1.3 channel at picomolar peptide concentration. The co-immunoprecipitation assays further supported the selective binding of hBD2 to Kv1.3 channel. Using mutagenesis experiments, we found that the outer pore domain of Kv1.3 channel was the binding site of hBD2, which is similar to the interacting site of Kv1.3 channel recognized by animal toxin inhibitors. The hBD2 was able to suppress IL-2 production through inhibition of Kv1.3 channel currents in human Jurkat cells, which was further confirmed by the lack of hBD2 activity on IL-2 production after Kv1.3 knockdown in these cells. More interestingly, hBD2 was also found to efficiently inhibit Kv1.3 channel currents and suppress IL-2 production in both human primary CD3(+) T cells and peripheral mononuclear cells from either healthy donors or psoriasis patients. Our findings not only evidenced hBD2 as the first characterized endogenous peptide inhibitor of human potassium channels, but also paved a promising avenue to investigate newly discovered function of hBD2 as Kv1.3 channel inhibitor in the immune system and other fields.