Last update 01 Nov 2024

GITR x IL-15

Last update 01 Nov 2024

Basic Info

Related Targets

GITRIL-15

Drugs associated with GITR x IL-15

MFA-021

Target

GITR x IL-15

Mechanism

GITR inhibitors [+1]

Active Org.

MediMabBio Co., Ltd.Startup

Originator Org.

MediMabBio Co., Ltd.Startup

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GITR x IL-15

100 Translational Medicine associated with GITR x IL-15

0 Patents (Medical) associated with GITR x IL-15

Literatures (Medical) associated with GITR x IL-15

15 Jun 2024·The Journal of Immunology

Generation of an Inhibitory NK Cell Subset by TGF-β1/IL-15 Polarization

Article

Author: Chung, Douglas C ; Bernardini, Marcus Q ; Nguyen, Linh T ; Elford, Alisha R ; Mathews, Jessica A ; Ohashi, Pamela S ; Wang, Ben X ; Clarke, Blaise A ; Crome, Sarah Q ; Sacher, Adrian G ; Wong, Stephanie W Y ; Shaw, Patricia A ; Garcia-Batres, Carlos R ; Millar, Douglas G

AbstractNK cells have been shown to exhibit inflammatory and immunoregulatory functions in a variety of healthy and diseased settings. In the context of chronic viral infection and cancer, distinct NK cell populations that inhibit adaptive immune responses have been observed. To understand how these cells arise and further characterize their immunosuppressive role, we examined in vitro conditions that could polarize human NK cells into an inhibitory subset. TGF-β1 has been shown to induce regulatory T cells in vitro and in vivo; we therefore investigated if TGF-β1 could also induce immunosuppressive NK-like cells. First, we found that TGF-β1/IL-15, but not IL-15 alone, induced CD103+CD49a+ NK-like cells from peripheral blood NK cells, which expressed markers previously associated with inhibitory CD56+ innate lymphoid cells, including high expression of GITR and CD101. Moreover, supernatant from ascites collected from patients with ovarian carcinoma also induced CD103+CD49a+ NK-like cells in vitro in a TGF-β–dependent manner. Interestingly, TGF-β1/IL-15–induced CD103+CD56+ NK-like cells suppressed autologous CD4+ T cells in vitro by reducing absolute number, proliferation, and expression of activation marker CD25. Collectively, these findings provide new insight into how NK cells may acquire an inhibitory phenotype in TGF-β1–rich environments.

01 Nov 2020·The FASEB JournalQ2 · BIOLOGY

GITR controls intestinal inflammation by suppressing IL‐15‐dependent NK cell activity

Q2 · BIOLOGY

Article

Author: So, Takanori ; Okuyama, Yuko ; Asao, Atsuko ; Ndhlovu, Lishomwa C. ; Riccardi, Carlo ; Kobayashi, Shuhei ; Sakurai, Tsuyoshi ; Nio, Masaki ; Ishii, Naoto ; Phung, Hai The ; Kudo, Hironori ; Kawabe, Takeshi ; Wada, Motoshi

Glucocorticoid-induced TNFR family related gene (GITR) is a member of the TNFR superfamily that is expressed on cells of the immune system. Although the protective and pathogenic roles of GITR in T cell immunity are well characterized, the role of GITR in innate immunity in the intestinal tissues has not been well clarified. In this study, using a dextran sulfate sodium (DSS)-induced colitis model in mice, we found that GITR-deficiency rendered mice more susceptible to acute intestinal inflammation and that a significantly higher number of activated natural killer (NK) cells was accumulated in the colonic lamina propria of Gitr^-/- mice as compared to wild-type mice. Additionally, Rag2^-/- Gitr^-/- mice, which lack T cells but have NK cells, also displayed more severe colonic inflammation than Rag2^-/- mice. In contrast, an anti-GITR agonistic antibody significantly alleviated colitis in Rag2^-/- mice. Engagement of GITR inhibited IL-15-mediated activating signaling events in NK cells, which include cell activation and proliferation, and production of cytokines and cytotoxic granules. Taken together, our results provide the first evidence that GITR negatively controls intestinal inflammation through NK cell functions.

28 Feb 2020·Bioscience ReportsQ4 · BIOLOGY

Comparative analysis of inflammatory signature profiles in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyposis

Q4 · BIOLOGY

Article

Author: Yao, Yao ; Sun, Hong ; Yi, Xing ; Yang, Chunguang ; Xie, Shaobing

AbstractChronic rhinosinusitis with nasal polyposis (CRSwNP) represents a heterogeneous disorder that can be classified into either eosinophilic or noneosinophilic endotypes. However, the immunological mechanisms of each remain unclear. The purpose of the present study was to compare and analyze inflammatory signatures of eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (NECRSwNP). Cytokine antibody array was used to identify inflammatory mediators that were differentially expressed among ECRSwNP, NECRSwNP, and control groups. Then, bioinformatics approaches were conducted to explore biological functions and signaling pathways. In addition, pairwise correlation analyses were performed among differential levels of inflammatory mediators and tissue eosinophil infiltration. The results showed that nine mediators were significantly up-regulated in ECRSwNP, including eotaxin-2, eotaxin-3, CCL18, IL-4, IL-5, IL-10, IL-12p70, IL-13, and IL-15. Bioinformatics analysis indicated that these mediators were mainly enriched in leukocyte chemotaxis and proliferation, JAK-STAT cascade, asthma, and Th1 and Th2 cell differentiation. Furthermore, seven mediators were identified to be significantly up-regulated in NECRSwNP, including CCL20, resistin, transforming growth factor (TGF)-β2, triggering receptor expressed on myeloid cells 1 (TREM-1), CD14, glucocorticoid-induced tumor necrosis factor receptor related protein (GITR), and lipocalin-2. These mediators were closely associated with LPS responses, neutrophil chemotaxis and migration, and IL-17 signaling pathway. In addition, pairwise correlation analyses indicated that differential levels of inflammatory mediators in ECRSwNP and NECRSwNP were broadly correlated with each other and with tissue eosinophil infiltration. In conclusion, we found that ECRSwNP and NECRSwNP exhibited different patterns of inflammatory signatures. These findings may provide further insights into heterogeneity of CRSwNP.

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