Last update 01 Nov 2024

IL-23 x CGRP

Last update 01 Nov 2024

Basic Info

Related Targets

IL-23CGRP

Drugs associated with IL-23 x CGRP

IL-23/CGRP bispecific antibody(Eli Lilly & Co.)

Target

CGRP x IL-23

Mechanism

CGRP antagonists [+1]

Active Org.

Eli Lilly & Co.

Originator Org.

Eli Lilly & Co.

Active Indication

Autoimmune Diseases

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with IL-23 x CGRP

100 Translational Medicine associated with IL-23 x CGRP

0 Patents (Medical) associated with IL-23 x CGRP

Literatures (Medical) associated with IL-23 x CGRP

01 Nov 2024·Nature Immunology

MrgprA3 neurons drive cutaneous immunity against helminths through selective control of myeloid-derived IL-33

Article

Author: Abdus-Saboor, Ishmail ; Freedman, Bruce D. ; Freedman, Bruce D ; Wu, Qinxue ; Femoe, Ulrich M ; Ferguson, Annabel A. ; Rossi, Heather L. ; Pastore, Christopher F ; Inclan-Rico, Juan M ; Reed, Danielle R ; Horák, Petr ; Napuri, Camila M ; Herbert, De’Broski R. ; Herbert, De'Broski R ; Luo, Wenqin ; Macháček, Tomáš ; Stephenson, Adriana ; Napuri, Camila M. ; Liu, Xiaohong ; Lin, Cailu ; Inclan-Rico, Juan M. ; Reed, Danielle R. ; Pastore, Christopher F. ; Rossi, Heather L ; Musaigwa, Fungai ; Femoe, Ulrich M. ; Ferguson, Annabel A ; Hung, Li-Yin

Skin uses interdependent cellular networks for barrier integrity and host immunity, but most underlying mechanisms remain obscure. Herein, we demonstrate that the human parasitic helminth Schistosoma mansoni inhibited pruritus evoked by itch-sensing afferents bearing the Mas-related G-protein-coupled receptor A3 (MrgprA3) in mice. MrgprA3 neurons controlled interleukin (IL)-17⁺ γδ T cell expansion, epidermal hyperplasia and host resistance against S. mansoni through shaping cytokine expression in cutaneous antigen-presenting cells. MrgprA3 neuron activation downregulated IL-33 but induced IL-1β and tumor necrosis factor in macrophages and type 2 conventional dendritic cells partially through the neuropeptide calcitonin gene-related peptide. Macrophages exposed to MrgprA3-derived secretions or bearing cell-intrinsic IL-33 deletion showed increased chromatin accessibility at multiple inflammatory cytokine loci, promoting IL-17/IL-23-dependent changes to the epidermis and anti-helminth resistance. This study reveals a previously unrecognized intercellular communication mechanism wherein itch-inducing MrgprA3 neurons initiate host immunity against skin-invasive parasites by directing cytokine expression patterns in myeloid antigen-presenting cell subsets.

01 Nov 2024·Journal of Ethnopharmacology

Artemisia argyi volatile oil ameliorates allergic contact dermatitis via modulating TRPA1/CGRP signaling

Article

Author: Zhao, Zhongqiu ; Wang, Mengling ; Xiong, Hui ; Mei, Zhinan ; He, Jinfeng ; Luo, Miao ; Yan, Ting ; Ma, Zhiliang

ETHNOPHARMACOLOGICAL RELEVANCEThe leaves of Artemisia argyi Levl.et Vant. have a long history of being used to treat skin diseases such as pruritus and dermatitis in China, but the therapeutic effect on allergic contact dermatitis (ACD) is still unclear.AIM OF THE STUDYTo investigate the effect and molecular mechanisms of the volatile oil of A. argyi leaves (abbreviated as 'AO') in the treatment of ACD.MATERIALS AND METHODSThe main components in AO were analyzed using GC-MS. The effect of AO on channel currents in hTRPA1-transfected HEK293T cells was studied by whole-cell patch clamp. Subsequently, chloroquine-evoked acute itch and squaraine dibutyl ester (SADBE)-induced ACD chronic itch model was established to evaluate the antipruritic effect through counting scratching behavior, and the anti-inflammatory effects on ACD mice were measured using histological analysis. Meanwhile, the changes of CGRP, the infiltration of nerve fibers and the recruitment of dendritic cells, the expression of Il-23 and Il-17 mRNA in skin lesions, the phosphorylation of ERK and p38 in dorsal root ganglion (DRG), were evaluated by molecular biological methods. Then the inhibitory effect of AO on AITC- or SADBE-activated TRPA1 channels in primary DRG neurons of C57BL/6, Trpa1^-/- or Trpv1^-/- mice was elucidated by Ca²⁺ imaging and immunofluorescence.RESULTSAO treatment inhibited the activation of TRPA1 in HEK293T cells and alleviated acute itch caused by chloroquine, but this effect was lacking in Trpa1^-/- mice. Furthermore, administration of AO attenuated scratching behavior in SADBE-induced ACD mice. AO also inhibited the increase of nerve fibers and recruitment of dendritic cells, and down-regulated the expression of CGRP and the levels of Il-23 and Il-17 mRNA. Meanwhile, AO reduced the expression of p-p38 and p-ERK in the lesioned skin and DRG of SADBE-induced ACD mice. Additionally, AO blocked the activation of TRPA1 channels and decreased the levels of CGRP, p-p38, and p-ERK in DRG neurons.CONCLUSIONAO could inhibit TRPA1 channels in sensory neurons, thereby reducing the release of CGRP and exerting anti-pruritic and anti-inflammatory effect. These findings also provide a new strategy for exploring the role of A. argyi in treating ACD.

01 Aug 2022·Journal of Investigative DermatologyQ1 · MEDICINE

Lidocaine Ameliorates Psoriasis by Obstructing Pathogenic CGRP Signaling‒Mediated Sensory Neuron‒Dendritic Cell Communication

Q1 · MEDICINE

Article

Author: Jiang, Bowen ; Tang, Sibei ; Song, Ningjing ; Zhou, Hong ; Yu, Buwei ; Sun, Yang ; Wu, Yue ; Cai, Xiaojie ; Wang, Bin ; Lou, Fangzhou ; Wang, Hong ; Li, Xia ; Wang, Zhikai ; Yin, Qianqian ; Sun, Libo ; Li, Qifang ; Bai, Jing ; Bao, Lan ; Wang, Honglin

Psoriasis is a chronic immune-mediated skin disorder with the nervous system contributing to its pathology. The neurogenic mediators of psoriasis are elusive, and whether the intervention of the cutaneous nervous system can treat psoriasis remains to be determined. In this study, we conducted a pilot study using an epidural injection of lidocaine to treat patients with psoriasis. Lidocaine treatment markedly reduced patients' clinical scores and improved an imiquimod-induced rat model of psoriasis as competent as systemic delivery of a TNF-α antibody. Imiquimod application elicited aberrant cutaneous nerve outgrowth and excessive generation of neuropeptide calcitonin gene-related peptide from dorsal root ganglion neurons, both of which were inhibited by epidural lidocaine treatment. Single-cell RNA sequencing unveiled the overrepresentation of calcitonin gene-related peptide receptors in dermal dendritic cell populations of patients with psoriasis. Through disturbing calcitonin gene-related peptide signaling, lidocaine inhibited IL-23 production by dendritic cells cocultured with dorsal root ganglion neurons. Thus, epidural nerve block with lidocaine demonstrates an effective therapy for psoriasis, which suppresses both inordinate sensory nerve growth in the inflamed skin and calcitonin gene-related peptide-mediated IL-23 production from psoriatic dendritic cells.

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