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Dual blockade of IL-17A and IL-36 pathways via a bispecific antibody exhibits enhanced anti-inflammatory potency.
Front Immunol
November 2024
Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China.
Antibody drugs targeting single inflammatory cytokines have revolutionized the treatment of immune-mediated inflammatory diseases. To investigate whether dual targeting interleukin-17 (IL-17) and IL-36 enhances anti-inflammatory activity, bispecific Ab HB0043 was generated by linking the single chain fragment variables (scFvs) from humanized anti-IL-36R antibody (HB0034) to the C-terminus of the heavy chain of anti-IL-17A IgG1 (HB0017) Fc using a flexible peptide linker. HB0043 largely maintained the binding affinities and biological activities of the two parent monoclonal antibodies (mAbs) .
View Article and Find Full Text PDFStructure-based design and disulfide stapling of interfacial cyclic peptidic inhibitors from thymic stromal lymphopoietin (TSLP) receptor to competitively target TSLP.
Biochimie
November 2024
Zhenjiang Hospital of Chinese Traditional and Western Medicine, Affiliated Zhenjiang Integrated Hospital of Traditional Chinese and Western Medicine of Xinglin College, Nantong University, Zhenjiang, 212000, China. Electronic address:
Human thymic stromal lymphopoietin (TSLP) is a pro-inflammatory cytokine located at the top of inflammatory cascade that makes it a promising therapeutic target in allergic asthma. The cell surface receptor of TSLP is a heterodimer consisting of a TSLP receptor (TSLPR) and an interleukin-17 receptor α (IL-7Rα). The TSLPR subunit should be first added to the free TSLP to form a TSLPR/TSLP pre-complex, which further recruits the IL-7Rα subunit to obtain the final TSLPR/IL-7Rα/TSLP complex.
View Article and Find Full Text PDFT17/Treg lymphocyte balance is regulated by beta adrenergic and cAMP signaling.
Brain Behav Immun
January 2025
Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, United States; Department of Medical Physiology, Texas A&M University, Bryan, TX, United States. Electronic address:
Background: Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that also presents with neuroimmune irregularities. Patients display elevated sympathetic tone and are at an increased risk of developing secondary autoimmune diseases. Previously, using a mouse model of repeated social defeat stress (RSDS) that recapitulates certain features of PTSD, we demonstrated that elimination of sympathetic signaling to T-lymphocytes specifically limited their ability to produce pro-inflammatory interleukin 17A (IL-17A); a cytokine implicated in the development of many autoimmune disorders.
View Article and Find Full Text PDF-derived vitamin B3 exerts protective effects against intestinal inflammation by promoting IL-17A/IL-22-dependent epithelial barrier function.
Gut Microbes
October 2024
Department of Life Science, National Taiwan University, Taipei, Taiwan.
a prevalent gut commensal fungus in healthy individuals - contributes to intestinal health and disease. However, how commensal influences intestinal homeostasis and barrier function is poorly understood. Here, we demonstrated that the reference strain of (MYA-3404) ameliorated intestinal inflammation in murine models of chemically induced colitis and bacterial infection.
View Article and Find Full Text PDFAPOE4 affects neutrophil-microglia crosstalk in Alzheimer's disease.
Trends Immunol
October 2024
Department of Medicine, University of Verona, Strada le Grazie 8, 37134 Verona, Italy; The Center for Biomedical Computing (CBMC), University of Verona, 37134 Verona, Italy. Electronic address:
Circulating immune cells contribute to the pathogenesis of Alzheimer's disease (AD), but their role is poorly understood. Rosenzweig et al. recently identified a subset of interleukin (IL)-17 neutrophils that inhibit neuroprotective microglia in female APOE4 carriers.
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