Last update 01 Nov 2024

CD40 x IFN Receptors

Last update 01 Nov 2024

Basic Info

Related Targets

CD40IFN Receptors

Drugs associated with CD40 x IFN Receptors

EVT-895

Target

CD40 x IFN Receptors

Mechanism

CD40 agonists [+1]

Active Org.

Evotec SE [+1]

Originator Org.

Evotec International GmbH [+2]

Active Indication

Hepatitis B

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CD40 x IFN Receptors

100 Translational Medicine associated with CD40 x IFN Receptors

0 Patents (Medical) associated with CD40 x IFN Receptors

Literatures (Medical) associated with CD40 x IFN Receptors

01 Dec 2024·Cellular and Molecular Life Sciences

Tyrosine kinase 2 modulates splenic B cells through type I IFN and TLR7 signaling

Article

Author: de Andrés, Belén ; Nicolao-Gómez, Ana ; Arrabal, Alejandro ; Jaén-Castaño, Marta ; Espadas, Cristina ; Martín-Gayo, Enrique ; Dopazo, Ana ; Fernández-Ruiz, Elena ; Bodega-Mayor, Irene ; Delgado-Wicke, Pablo ; Alegría-Carrasco, Estíbaliz ; Gaspar, María Luisa

AbstractTyrosine kinase 2 (TYK2) is involved in type I interferon (IFN-I) signaling through IFN receptor 1 (IFNAR1). This signaling pathway is crucial in the early antiviral response and remains incompletely understood on B cells. Therefore, to understand the role of TYK2 in B cells, we studied these cells under homeostatic conditions and following in vitro activation using Tyk2-deficient (Tyk2−/−) mice. Splenic B cell subpopulations were altered in Tyk2−/− compared to wild type (WT) mice. Marginal zone (MZ) cells were decreased and aged B cells (ABC) were increased, whereas follicular (FO) cells remained unchanged. Likewise, there was an imbalance in transitional B cells in juvenile Tyk2−/− mice. RNA sequencing analysis of adult MZ and FO cells isolated from Tyk2−/− and WT mice in homeostasis revealed altered expression of IFN-I and Toll-like receptor 7 (TLR7) signaling pathway genes. Flow cytometry assays corroborated a lower expression of TLR7 in MZ B cells from Tyk2−/− mice. Splenic B cell cultures showed reduced proliferation and differentiation responses after activation with TLR7 ligands in Tyk2−/− compared to WT mice, with a similar response to lipopolysaccharide (LPS) or anti-CD40 + IL-4. IgM, IgG, IL-10 and IL-6 secretion was also decreased in Tyk2−/− B cell cultures. This reduced response of the TLR7 pathway in Tyk2−/− mice was partially restored by IFNα addition. In conclusion, there is a crosstalk between TYK2 and TLR7 mediated by an IFN-I feedback loop, which contributes to the establishment of MZ B cells and to B cell proliferation and differentiation.

01 Jun 2024·Biotechnology Letters

In silico designing of novel epitope-based peptide vaccines against HIV-1

Article

Author: Namdari, Haideh ; Arjmand, Sina ; Sadat, Seyed Mehdi ; Namvar, Ali ; Rezaei, Fatemeh ; Bolhassani, Azam ; Heidarnejad, Fatemeh ; Pordanjani, Parisa Moradi

The HIV-1 virus has been regarded as a catastrophe for human well-being. The global incidence of HIV-1-infected individuals is increasing. Hence, development of effective immunostimulatory molecules has recently attracted an increasing attention in the field of vaccine design against HIV-1 infection. In this study, we explored the impacts of CD40L and IFN-γ as immunostimulatory adjuvants for our candidate HIV-1 Nef vaccine in human and mouse using immunoinformatics analyses. Overall, 18 IFN-γ-based vaccine constructs (9 constructs in human and 9 constructs in mouse), and 18 CD40L-based vaccine constructs (9 constructs in human and 9 constructs in mouse) were designed. To find immunogenic epitopes, important characteristics of each component (e.g., MHC-I and MHC-II binding, and peptide-MHC-I/MHC-II molecular docking) were determined. Then, the selected epitopes were applied to create multiepitope constructs. Finally, the physicochemical properties, linear and discontinuous B cell epitopes, and molecular interaction between the 3D structure of each construct and CD40, IFN-γ receptor or toll-like receptors (TLRs) were predicted. Our data showed that the full-length CD40L and IFN-γ linked to the N-terminal region of Nef were capable of inducing more effective immune response than multiepitope vaccine constructs. Moreover, molecular docking of the non-allergenic full-length- and epitope-based CD40L and IFN-γ constructs to their cognate receptors, CD40 and IFN-γ receptors, and TLRs 4 and 5 in mouse were more potent than in human. Generally, these findings suggest that the full forms of these adjuvants could be more efficient for improvement of HIV-1 Nef vaccine candidate compared to the designed multiepitope-based constructs.

03 Jul 2023·Scientific reports

Higher CD4⁺CD40⁺ T cells (Th40 cells) associate with systemic lupus erythematosus activity.

Article

Author: Cui, Yanjie ; Liu, Xiaoen ; Zhang, Yue ; Li, Xueqin ; Wang, Liang ; Li, Bo ; Song, Guangmei ; Li, Yangqiu ; Chen, Xiaohui ; Zeng, Xiangbo ; Zhu, Lihua ; Qiao, Jie ; Huang, Xinran

The aim of this study was to investigate the characteristics of CD4⁺CD40⁺ T cells (Th40 cells) in Chinese systemic lupus erythematosus (SLE) patients. Flow cytometry was used to identify the percentage of Th40 cells in peripheral blood from 24 SLE patients and 24 healthy individuals and the level of IL-2, IL-4, IL-6, IL-10, IFN-r, and TNF-α in serum (22 cases) from the SLE patients. Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) was used to assess the SLE disease active state. The percentage of Th40 cells in T cells from SLE patients (19.37 ± 17.43) (%) was significantly higher than that from healthy individuals (4.52 ± 3.16) (%) (P < 0.001). The percentage of Th40 cells was also positively associated with SLEDAI-2000 (P = 0.001) and negatively associated with complement C3 (P = 0.007). The Th40 cell percentage was different in SLE patients with different organs involved. The Th40 cell percentage in SLE patients with lupus serositis (29.29 ± 22.19) was significantly higher than that in patients without serositis (13.41 ± 10.79; P = 0.040), and the percentage in SLE patients with lupus pneumonia involvement (29.11 ± 11.88) was significantly higher than that in patients without lupus pneumonia (16.80 ± 17.99; P = 0.043). After 4 weeks treatment, the Th40 cell percentage decreased significantly (P = 0.005). However, Th40 cell expression was not related to cytokines (IL-2, IL-4, IL-6, IL-10, IFN-r, and TNF-α; P > 0.05). A significantly higher percentage of Th40 cells was found in SLE patients, and the Th40 cell percentage was associated with SLE activity. Thus, Th40 cells may be used as a predictor for SLE disease activity and severity and therapeutic efficacy.

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