Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma

Hill, Geoffrey R.; Olver, Stuart D.; Kuns, Rachel D.; Varelias, Antiopi; Raffelt, Neil C.; Don, Alistair L. J.; Markey, Kate A.; Wilson, Yana A.; Smyth, Mark J.; Iwakura, Yoichiro; Tocker, Joel; Clouston, Andrew D.; MacDonald, Kelli P. A.

doi:10.1182/blood-2009-11-256495

Cited by 143 publications

(150 citation statements)

References 48 publications

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“…These data are consistent with a large number of recent studies conducted in mice that concluded that Th17 cells are implicated in GVHD development in mice. Among them, a study reported that amplification of IL-17 production by the use of the stem cell mobilization factor G-CSF leads to a cutaneous fibrosis occurring late after the graft, as in Scl-GVHD (21). Consistent with those data, another recent article stated that the use of an anti-IL-17 mAb can ameliorate skin symptoms in chronic GVHD (20,26).…”

Section: Discussionmentioning

confidence: 80%

“…In addition, we explored the splenic production of IL-4 and IL-17, two cytokines implicated in the development of GVHD in mice (21). Scl-GVHD mice produced more IL-4 and IL-17 than did control mice (IL-4: 0.24 6 0.023 for Scl-GVHD mice and 0.12 6 0.021 for control mice, p = 0.011; IL-17: 0.64 6 0.083 for Scl-GVHD mice and 0.37 6 0.088 for control mice, p = 0.042; Fig.…”

Section: As 2 O 3 Prevented Clinical Symptoms Of Systemic Sclerosis Imentioning

confidence: 99%

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Arsenic Trioxide Prevents Murine Sclerodermatous Graft-versus-Host Disease

Kavian

Marut

Servettaz

et al. 2012

The Journal of Immunology

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Chronic graft-versus-host disease (GVHD) follows allogeneic hematopoietic stem cell transplantation. It results from alloreactive processes induced by minor MHC incompatibilities triggered by activated APCs, such as plasmacytoid dendritic cells (pDCs), and leading to the activation of CD4 T cells. Therefore, we tested whether CD4+ and pDCs, activated cells that produce high levels of reactive oxygen species, could be killed by arsenic trioxide (As2O3), a chemotherapeutic drug used in the treatment of acute promyelocytic leukemia. Indeed, As2O3 exerts its cytotoxic effects by inducing a powerful oxidative stress that exceeds the lethal threshold. Sclerodermatous GVHD was induced in BALB/c mice by body irradiation, followed by B10.D2 bone marrow and spleen cell transplantation. Mice were simultaneously treated with daily i.p. injections of As2O3. Transplanted mice displayed severe clinical symptoms, including diarrhea, alopecia, vasculitis, and fibrosis of the skin and visceral organs. The symptoms were dramatically abrogated in mice treated with As2O3. These beneficial effects were mediated through the depletion of glutathione and the overproduction of H2O2 that killed activated CD4+ T cells and pDCs. The dramatic improvement provided by As2O3 in the model of sclerodermatous GVHD that associates fibrosis with immune activation provides a rationale for the evaluation of As2O3 in the management of patients affected by chronic GVHD.

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Section: Discussionmentioning

confidence: 80%

Section: As 2 O 3 Prevented Clinical Symptoms Of Systemic Sclerosis Imentioning

confidence: 99%

Arsenic Trioxide Prevents Murine Sclerodermatous Graft-versus-Host Disease

Kavian

Marut

Servettaz

et al. 2012

The Journal of Immunology

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“…This effect is perhaps most prominent in interleukin-17 (IL-17)-producing donor T cells, which we and others have shown to be highly pathogenic in preclinical models of GVHD. [1][2][3][4][5][6] Plasticity has been widely reported in CD4 IL-17A 1 (Tc17) T cells in a range of infectious and autoimmune settings. [6][7][8][9][10][11][12] We have recently described Tc17 cytokine plasticity in murine allo-SCT recipients, 1 which is characteristic of a hyper-proinflammatory T-cell subset that contributes to GVHD but fails to mediate graft-versus-leukemia effects.…”

Section: Introductionmentioning

confidence: 99%

Th17 plasticity and transition toward a pathogenic cytokine signature are regulated by cyclosporine after allogeneic SCT

et al. 2017

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“…The use of G-CSF for collecting PBSC grafts causes an amplification of IL-17 and that process has a major role in sclerosis after allogeneic PBSC transplantation. 22 This observation in murine model needs further immunological investigations in human to be confirmed.…”

Section: Discussionmentioning

confidence: 86%

Pre-transplantation risk factors to develop sclerotic chronic GvHD after allogeneic HSCT: A multicenter retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Detrait

Morisset

Latour

et al. 2014

Bone Marrow Transplant

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Sclerotic chronic GvHD (cGvHD) is one of the most severe complications after allo-hematopoietic stem cell transplantation (HSCT). Risk factors associated with this complication remain not very well defined. With the aim to define a pre-transplantation risk profile, we have conducted a French retrospective analysis in 705 consecutive patients between 2005 and 2010. Analyses to determine pre-transplantation risk factors included as variables: patient and donor age, kind of donor, HLA matching, ABO matching, sex-matching, diagnosis, stem cell source, gender, GvHD prophylaxis and antithymocyte globulin (ATG) in the conditioning regimen. The cumulative incidence of sclerotic cGvHD was 18% (95% CI, 16.6-19.6) 3 years after onset of cGvHD. In univariate analysis, we found a significantly lower number of sclerotic cGvHD form in patients transplanted from cord blood cells (P = 0.0021), in patients with a one mismatched donor (P =0. 041) and in patients who had received ATG in the conditioning regimen (P = 0.002). In multivariate analysis, factors associated with an increased risk of sclerotic cGvHD were young patient age, multiple myeloma and PBSC as the stem cell source. ATG in conditioning regimen and cord blood unit as the stem cell source were associated with a lower risk.

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Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma

Cited by 143 publications

References 48 publications

Arsenic Trioxide Prevents Murine Sclerodermatous Graft-versus-Host Disease

Arsenic Trioxide Prevents Murine Sclerodermatous Graft-versus-Host Disease

Th17 plasticity and transition toward a pathogenic cytokine signature are regulated by cyclosporine after allogeneic SCT

Pre-transplantation risk factors to develop sclerotic chronic GvHD after allogeneic HSCT: A multicenter retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

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