异基因造血干细胞移植后早期给予来那度胺通过抑制 T 细胞向胃肠道迁移来抑制移植物抗宿主病

We analyzed the lymphocyte composition in naïve mice treated with LEN. Subsequently, we treated host mice with LEN, soon after aHSCT, and analyzed GVHD severity as well as the composition and characteristics of lymphocytes associated with GVHD.

Using a mouse model, we demonstrated the beneficial effects of LEN for treating acute GVHD. Although natural killer cells were slightly increased by LEN, it did not significantly change T-cell proliferation and the balance of the T-cell subset in naïve mice. LEN did not modulate the suppressive function of regulatory T cells (Tregs). Unexpectedly, LEN prevented severe GVHD in a mouse acute GVHD model. Donor-derived lymphocytes were more numerous in host mice treated with LEN than in host mice treated with vehicle. Lymphocyte infiltration of the gastrointestinal tract in host mice treated with LEN was less severe compared to that in host mice treated with vehicle. The percentage of LPAM-1 (α 4 β 7 -integrin)-expressing Foxp3 - CD4 + T cells was significantly lower in host mice treated with LEN than in host mice treated with vehicle, whereas that of LPAM-1-expressing Tregs was comparable.

LEN may be useful as a prophylactic agent for acute GVHD-induced mortality through the inhibition of lymphocyte migration to the gastrointestinal tract. Our data show the effect of LEN on immune responses early after aHSCT and suggest that cereblon, a molecular target of LEN, may be a therapeutic target for preventing acute GVHD-induced mortality.