In:
The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 1_Supplement ( 2015-05-01), p. 185.12-185.12
Abstract:
Scleroderma is an autoimmune disease characterized by inflammation and fibrosis in skin and internal organs. We utilized a murine Graft Versus Host Disease (GVHD) model of Scleroderma (SclGVHD), in which lymphocytes are transferred from B10.D2 mice (graft) into MHC-matched, lymphocyte deficient Balb/c Rag2-/- mice (host, sclGVHD mice). Over the course of 6 weeks, sclGVHD mice develop skin inflammation and fibrosis. Previously, we identified IL13 pathway activation in the skin of sclGVHD mice and scleroderma patients. Accordingly, host mice lacking IL4RA, a functional subunit for the IL13 receptor complex, are protected from sclGVHD. Here, we show that sclGVHD-IL4Ra-/- mice display a defect in lymphocyte trafficking, with more activated T cells in subcutaneous lymph nodes (sLNs) but fewer T cells in lymph, blood and skin compared to control mice. In addition, sphingosine 1-phosphate (S1P) kinase 1 was decreased in the sLNs and in sorted lymphatic endothelial cells (LEC) from sclGVHD-IL4Ra-/- mice. Since S1P is the major regulator of lymphocyte egress from sLNs, these data suggest that IL4Ra promotes sclGVHD by inducing the production of this mediator from LECs, which drives activated T cells into the periphery. These experiments highlight a potential novel role for IL4RA in inflammatory diseases, and indicate that strategies which impede lymphocyte trafficking may be effective therapeutically in the context of GVHD and scleroderma.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.194.Supp.185.12
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2015
detail.hit.zdb_id:
1475085-5
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