A critical role for donor-derived IL-22 in cutaneous chronic GVHD

Gartlan, Kate H., Bommiasamy, Hemamalini, Paz, Katelyn, Wilkinson, Andrew N., Owen, Mary, Reichenbach, Dawn K., Banovic, Tatjana, Wehner, Kimberly, Buchanan, Faith, Varelias, Antiopi, Kuns, Rachel D., Chang, Karshing, Fedoriw, Yuri, Shea, Thomas, Coghill, James, Zaiken, Michael, Plank, Maximilian W., Foster, Paul S., Clouston, Andrew D., Blazar, Bruce R., Serody, Jonathan S. and Hill, Geoffrey R. (2017) A critical role for donor-derived IL-22 in cutaneous chronic GVHD. American Journal of Transplantation , . doi:10.1111/ajt.14513

Author Gartlan, Kate H.
Bommiasamy, Hemamalini
Paz, Katelyn
Wilkinson, Andrew N.
Owen, Mary
Reichenbach, Dawn K.
Banovic, Tatjana
Wehner, Kimberly
Buchanan, Faith
Varelias, Antiopi
Kuns, Rachel D.
Chang, Karshing
Fedoriw, Yuri
Shea, Thomas
Coghill, James
Zaiken, Michael
Plank, Maximilian W.
Foster, Paul S.
Clouston, Andrew D.
Blazar, Bruce R.
Serody, Jonathan S.
Hill, Geoffrey R.
Title A critical role for donor-derived IL-22 in cutaneous chronic GVHD
Journal name American Journal of Transplantation    Check publisher's open access policy
ISSN 1600-6143
Publication date 2017-10-24
Year available 2017
Sub-type Article (original research)
DOI 10.1111/ajt.14513
Open Access Status Not yet assessed
Total pages 11
Place of publication Hoboken, NJ United States
Publisher Wiley-Blackwell Publishing
Abstract Graft-versus-host disease (GVHD) is the major cause of nonrelapse morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). Prevention and treatment of GVHD remain inadequate and commonly lead to end-organ dysfunction and opportunistic infection. The role of interleukin (IL)-17 and IL-22 in GVHD remains uncertain, due to an apparent lack of lineage fidelity and variable and contextually determined protective and pathogenic effects. We demonstrate that donor T cell-derived IL-22 significantly exacerbates cutaneous chronic GVHD and that IL-22 is produced by highly inflammatory donor CD4(+) T cells posttransplantation. IL-22 and IL-17A derive from both independent and overlapping lineages, defined as T helper (Th)22 and IL-22(+) Th17 cells. Donor Th22 and IL-22(+) Th17 cells share a similar IL-6-dependent developmental pathway, and while Th22 cells arise independently of the IL-22(+) Th17 lineage, IL-17 signaling to donor Th22 directly promotes their development in allo-SCT. Importantly, while both IL-22 and IL-17 mediate skin GVHD, Th17-induced chronic GVHD can be attenuated by IL-22 inhibition in preclinical systems. In the clinic, high levels of both IL-17A and IL-22 expression are present in the skin of patients with GVHD after allo-SCT. Together, these data demonstrate a key role for donor-derived IL-22 in patients with chronic skin GVHD and confirm parallel but symbiotic developmental pathways of Th22 and Th17 differentiation.
Keyword T cell biology
basic (laboratory) research/science
bone marrow/hematopoietic stem cell transplantation
bronchiolitis obliterans (BOS)
cytokines/cytokine receptors
graft-versus-host disease (GVHD)
lymphocyte biology: differentiation/maturation
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID P01 CA142106
R01 CA166794
T32 AI007313
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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School of Medicine Publications
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Created: Wed, 15 Nov 2017, 12:21:48 EST