CXCL10-CXCR3 interactions play an important role in the pathogenesis of acute graft-versus-host disease in the skin following allogeneic stem-cell transplantation

Piper, Kim; Horlock, Claire; Curnow, S. John; Arrazi, Julie; Nicholls, Sarah; Mahendra, Premini; Craddock, Charles; Moss, Paul

doi:10.1182/blood-2006-12-061408

Cited by 109 publications

(93 citation statements)

References 25 publications

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“…[24][25][26][27][28][29][30][31][32][33][34][35] The wide discrepancies may be attributable to the diversity of the diseases transplanted, the transplant conditioning (notably inclusion of antithymocyte globulin); 23 genetic diversity, including cytokine (receptor) gene polymorphisms, [36][37][38][39][40] infection, veno-occlusive disease and lymphocytopenia in the case of transient IL-7 and IL-15 increases. [3][4][5][6]29,41,42 However, the achievement of full lymphoid chimerism has so far not been identified as a significant moment for cytokine changes.…”

Section: Discussionmentioning

confidence: 99%

Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation

Melenhorst

Tian

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundAllogeneic hematopoietic stem cell transplantation is associated with profound changes in levels of various cytokines. Emphasis has been placed on conditioning-associated mucosal damage and neutropenia and associated bacterial translocation as the initiating conditions predisposing to acute graft-versus-host disease. The post-transplant period is, however, also associated with increases in certain homeostatic cytokines. It is unclear how much the homeostatic drive to lymphocyte recovery and the production of cytokines from the engrafting donor immune system determine cytokine fluctuations in the peri-and immediate post-transplant period. The aim of this study was to examine the contributions of the conditioning regimen, donor engraftment, infections, and graft-versus-host disease to fluctuations in cytokines involved in homeostasis and inflammation. Design and MethodsWe examined the levels of 33 cytokines in relation to peri-and post-transplant events such as conditioning regimen, chimerism, and acute graft-versus-host disease in myeloablative, non-T cell-replete HLA-identical sibling donor stem cell transplantation for hematologic malignancies. ResultsWe identified two cytokine storms. The first occurred following conditioning and reached peak levels when all the leukocytes were at their lowest concentrations. The second cytokine storm occurred concurrently with hematopoietic reconstitution and subsided with the achievement of full donor lymphocyte chimerism. ConclusionsOur results indicate that both recipient-related and donor-related factors contribute to the changes in cytokine levels in the recipient following allogeneic hematopoietic stem cell transplantation. The study reported here was performed using plasma samples drawn from patients enrolled in the ClinicalTrials.gov-registered trials NCT00467961 and NCT00378534

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Section: Discussionmentioning

confidence: 99%

Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation

Melenhorst

Tian

et al. 2011

Haematologica

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“…[30][31][32] In the skin with aGVHD patients, IP-10 expression was observed in the basal tinocytes of the epidermis and CXCR3 was on cells in dermal infiltrates, otherwise IL-4 was not increased in the serum from aGVHD. 33 However, relatively little is still known about it in cGVHD. From the results obtained in the present study, we consider that the interaction of CXCR3 and/or CCR5 with IP-10 might have an important role in the migration of Th1 cells and then in the initiation and/or maintenance of cGVHD.…”

Section: Cytokines Chemokines and Chemokine Receptors Involvement Inmentioning

confidence: 99%

Possible involvement of cytokines, chemokines and chemokine receptors in the initiation and progression of chronic GVHD

Nakamura

Toyoshima

Moriyama

et al. 2012

Bone Marrow Transplant

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Chronic GVHD (cGVHD) after allogeneic hematopoietic SCT (HSCT) is characterized by an infiltration of T cells into target organs including the oral mucosa and salivary glands. This study was designed to clarify the molecular mechanism of the local accumulation of pathogenic T cells in cGVHD. The expression of cytokines, chemokines and chemokine receptors in the buccal mucosa (BM), labial salivary glands (LSG) and PBMC from 16 patients with cGVHD after allogeneic HSCT was examined. The mRNA expression of T helper 1 (Th1) and Th2 cytokines, and several chemokines and chemokine receptors was significantly increased in the BM and LSG from cGVHD patients, in comparison with both those in the BM and LSG from controls, respectively, and also with those in the PBMC from cGVHD patients. Furthermore, the mRNA expression of Th2 cytokines, macrophage-derived chemokine and CC chemokine receptor 4 was closely associated with a strong T-cell infiltration in the BM and LSG from cGVHD patients. These results suggest that cGVHD might be initiated and/or maintained by Th1/Th0 cells and thereafter progresses in association with Th2 cell accumulation via the interaction of particular chemokine and chemokine receptors.

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“…Chemokines, which are small molecules that bind to a family of heterotrimeric G proteins and participate in lymphocyte trafficking, are also being studied. Piper et al 34 performed a prospective analysis in 34 patients after HCT and showed a two-fold increase in serum levels of the chemokine CXCL10 in patients with acute GVHD relative to control patients. Hori et al 35 used a proteomics approach in murine models of HCT to identify serum levels of the chemokine CCL8.…”

Section: Il-2mentioning

confidence: 99%

“…34 Hori et al 35 Abbreviations: CRP ¼ C-reactive protein; CCL8 ¼ C-C motif ligand 8; CXCL10 ¼ C-X-C motif chemokine 10; HGF ¼ hepatocyte growth factor; NK ¼ natural killer; sCD30 ¼ soluble CD30; TGF ¼ transforming growth factor.…”

Section: Cxcl10 Ccl8mentioning

confidence: 99%

Biomarkers for acute GVHD: can we predict the unpredictable?

2012

Bone Marrow Transplant

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Acute GVHD remains an important complication after allogeneic hematopoietic cell transplantation (HCT). Many efforts have been devoted to identifying potential noninvasive peripheral blood biomarkers to help improve the diagnosis or management of acute GVHD while avoiding invasive tissue biopsies. Early attempts to identify biomarkers focused on inflammatory cytokines, especially IL-2 or TNF-a, however, both of these and others were not specific for GVHD, often being elevated in the setting of generalized inflammation, accompanying other major complications of HCT as well. More recent efforts have focused on additional cytokines and other cell-surface molecules, which function in leukocyte trafficking and activation with the hope that these can also serve as targets for novel therapeutic approaches. Modern proteomic methods have allowed the screening of large numbers of patient samples and yielded several novel candidate biomarkers, including elafin and reg3a, which may not be directly involved in the immunological pathogenesis of GVHD, but may be unique biomarkers for end-organ injury. Combining these new molecules with traditionally identified cytokines to form an acute GVHD biomarker panel has recently shown the ability to predict outcomes in patients who develop acute GVHD. The ultimate goals of identifying a specific biomarker are to refine diagnosis, guide therapy and develop risk-adapted approaches in order to better treat patients and improve outcomes after allogeneic HCT. These approaches include differential treatment for patients who develop acute GVHD with a high-risk biomarker profile as well as pre-emptive therapy in patients after HCT prior to the development of symptoms. With the recent progress summarized below, these goals may soon be realized.

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CXCL10-CXCR3 interactions play an important role in the pathogenesis of acute graft-versus-host disease in the skin following allogeneic stem-cell transplantation

Cited by 109 publications

References 25 publications

Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation

Cytopenia and leukocyte recovery shape cytokine fluctuations after myeloablative allogeneic hematopoietic stem cell transplantation

Possible involvement of cytokines, chemokines and chemokine receptors in the initiation and progression of chronic GVHD

Biomarkers for acute GVHD: can we predict the unpredictable?

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