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A critical role for donor‐derived IL ‐22 in cutaneous chronic GVHD
Author(s) -
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.
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14513
Subject(s) - medicine , immunology , graft versus host disease , interleukin 22 , stem cell , interleukin 17 , disease , transplantation , immune system , interleukin , cytokine , biology , genetics
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 CD 4 + 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.