Only Therapeutic ICOS:ICOSL Blockade Alleviates Acute Graft versus Host Disease

Mollweide, Andreas; Staege, Martin S.; Hoeschen, Christoph; Yano, Hideo; Burdach, Stefan; Richter, Günther

doi:10.1055/s-0029-1239532

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…Our observations are consistent with previous reports that blockade of ICOS/ICOS-ligand interaction ameliorated acute and chronic GVHD 28 , 46 – 48 . On the other hand, our experiments have unraveled the role of ICOS/ICOS-ligand interaction in augmenting expansion of extrafollicular PSGL-1 lo CD4 + T cells.…”

Section: Discussionsupporting

confidence: 93%

Extrafollicular CD4+ T-B interactions are sufficient for inducing autoimmune-like chronic graft-versus-host disease

et al. 2017

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Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome mediated by pathogenic CD4+ T and B cells, but the function of extrafollicular and germinal center CD4+ T and B interactions in cGVHD pathogenesis remains largely unknown. Here we show that extrafollicular CD4+ T and B interactions are sufficient for inducing cGVHD, while germinal center formation is dispensable. The pathogenesis of cGVHD is associated with the expansion of extrafollicular CD44hiCD62loPSGL-1loCD4+ (PSGL-1loCD4+) T cells. These cells express high levels of ICOS, and the blockade of ICOS/ICOSL interaction prevents their expansion and ameliorates cGVHD. Expansion of PSGL-1loCD4+ T cells is also prevented by BCL6 or Stat3 deficiency in donor CD4+ T cells, with the induction of cGVHD ameliorated by BCL6 deficiency and completely suppressed by Stat3 deficiency in donor CD4+ T cells. These results support that Stat3- and BCL6-dependent extrafollicular CD4+ T and B interactions play critical functions in the pathogenesis of cGVHD.

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Section: Discussionsupporting

confidence: 93%

Extrafollicular CD4+ T-B interactions are sufficient for inducing autoimmune-like chronic graft-versus-host disease

et al. 2017

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“…This is the first example of efficacy of anti-ICOS mAb in treating chronic GVHD in a large outbred animal model. Earlier studies in mice suggested that ICOS:ICOSL blockade could alleviate GVHD [15–17]. However, studies specifically addressing chronic GVHD were limited.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inducible Costimulator Monoclonal Antibody Treatment of Canine Chronic Graft-versus-Host Disease

Graves

Parker

Stone

et al. 2018

Biology of Blood and Marrow Transplantation

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In murine model systems inducible costimulator (ICOS) signaling has been implicated in the formation of chronic graft-versus-host disease (GVHD). Previously, we showed that chronic GVHD can be reproducibly produced in the dog hematopoietic cell transplantation (HCT) model and that ICOS expression is upregulated on T cells in dogs with chronic GVHD. The goal of the present study was to determine whether administration of a short course of anti-canine ICOS mAb could alter the rapid and progressive course of chronic GVHD. Five dogs underwent HCT from dog leukocyte antigen mismatched unrelated donors after total body irradiation. Postgrafting immunosuppression consisted of methotrexate (days 1, 3, 6, and 11) and cyclosporine (days -1 through 78). Anti-ICOS mAb (3 injections, 72 hours apart) was administered upon diagnosis of GVHD. One dog failed to respond to anti-ICOS mAb therapy and succumbed to chronic GVHD in a time course similar to control untreated dogs. Overall, anti-ICOS-treated dogs experienced a significant prolongation in survival from the time of diagnosis of chronic GVHD compared with control dogs. Within the limitations of the number of study dogs we suggest that a short course of anti-ICOS mAb may be useful in the treatment of chronic canine GVHD.

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“…As the second signaling, ICOS/ICOSL costimulatory signaling is necessary for the homeostasis and function of various immune cell populations, and plays different roles in a series of disease models [24][25][26].…”

Section: Discussionmentioning

confidence: 99%

IL-33 Involved in the Progression of Liver Fibrosis Through Innate Immunity Cells (Mφ) Regulated by ICOS/ICOSL Signaling in Early Stage of Mice Schistosomiasis

Liu

Wang

Xie

et al. 2022

Preprint

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Schistosomiasis liver fibrosis is characterized by the foci of a classical type 2 granulomatous inflammation in response to egg soluble antigen. The inducible costimulator (ICOS)/ICOSL signaling can mediate Th2 polarization and regulate the disease process of chronic schistosomiasis by adaptive immune response. ICOS/ICOSL signaling could regulate innate immune cells, including B cells and macrophage (Mϕ), and participate in pulmonary fibrosis. The purpose of the study was to identify whether ICOS/ICOSL signaling could regulate the polarization of Mϕ, and to explore the potential role of IL-33 in ICOSL knockout (ICOSL-KO) mice with schistosomiasis. Firstly, the expression level of CD86, CD206 and IL-33 was checked respectively in ICOSL-KO and WT mice infected with Schistosoma japonicum (S. japonicum). Then recombinant IL-33 (rIL-33) was injected into ICOSL-KO mice infected with S. japonicum. Our experiments showed that the liver Mϕ was successfully polarized toward to classical activated Mϕ and the expression of IL-33 was inhibited in ICOSL-KO mice. Furthermore, the injection of rIL-33 successfully aggravated liver fibrosis in ICOSL-KO mice, increased the numbers of lymphocyte antigen 6C (Ly6C) hi, enhanced the expression of C-C chemokine ligand (CCL)2, CCL5 and C-X-C motif chemokine 2 (CXCL2), and promoted polarization of T helper (Th) cells to Th2 cells, as well as induced the autophagy and apoptosis of hepatic stellate cells (HSCs). Overall, the liver fibrosis was alleviated in ICOSL-KO mice along with the reduced expression of IL-33, which could skew the polarization of Mϕ toward to M1, induce Th cells activation, HSCs apoptosis and autophagy through Smad2/3 and TGF-β signaling pathway, thus participated in the homeostasis of liver fibrosis of schistosomiasis.

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Only Therapeutic ICOS:ICOSL Blockade Alleviates Acute Graft versus Host Disease

Cited by 8 publications

References 26 publications

Extrafollicular CD4+ T-B interactions are sufficient for inducing autoimmune-like chronic graft-versus-host disease

Extrafollicular CD4+ T-B interactions are sufficient for inducing autoimmune-like chronic graft-versus-host disease

Anti-Inducible Costimulator Monoclonal Antibody Treatment of Canine Chronic Graft-versus-Host Disease

IL-33 Involved in the Progression of Liver Fibrosis Through Innate Immunity Cells (Mφ) Regulated by ICOS/ICOSL Signaling in Early Stage of Mice Schistosomiasis

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