Abstract book (download .pdf file) - Redox and Inflammation ...

Gimap5: a critical mediator of lymphocyte homeostasis and determinant of autoinflammatory
disease.
Halil Aksoylar, Michael J Barnes, and Kasper Hoebe
Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio, USA
Homeostatic control of the immune system involves mechanisms that ensure the selftolerance,
survival and quiescence of hematopoietic-derived cells. Previous reports linked
genetic aberrancies in the GTPase the immunity-associated protein 5 (Gimap5) to autoimmune
disorders in both humans and rats, suggesting that Gimap5 is an important mediator
of immune homeostasis. Our laboratory recently identified a recessive ENU-induced germline
mutation that destabilizes Gimap5. Homozygote mutant mice develop lymphopenia, hepatic
extramedullary hematopoiesis, weight loss and intestinal inflammation. Although Gimap5deficient
CD4 + T and B cells undergo normal development, they fail to proliferate upon
antigen-receptor stimulation even though NF-!B, MAP kinase and Akt activation occur
normally. Activation of CD4 + T cells results in normal cytokine secretion predominantly
polarized towards TH17. In addition mutant mice contain reduced numbers of peripheral Treg
cells that also exhibit a reduced suppressive capacity compared to wildtype Treg cells.
Together, these data establish Gimap5 as a key regulator of hematopoietic integrity and
lymphocyte homeostasis.
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