Leukaemia Inhibitory Factor (LIF) is a Treg cytokine (141.35)

Abstract Priming of the T lymphocyte results in either regulatory (Treg), or effector (Teff), lineage development. During priming the immediate micro-environment contributes to outcome and LIF, a pluripotent cytokine of the IL6 family, appears to be linked to Treg: in contrast IL6 is associated with Teff. Here we ask, is LIF a Treg cytokine? We found in vitro (i) exogenous LIF (10ng/ml) increased transcription of both Foxp3 - the Treg lineage transcription factor - and LIF: and (ii) when naive CD4+ Foxp3- T cells were activated by anti-CD3/anti-CD28, the presence of exogenous LIF enhanced numbers of Foxp3+ cells. We therefore asked, can LIF be used as a tolerogenic therapy? To avoid LIF's rapid degradation by serum proteases we developed a delivery system wherein LIF was encapsulated within nanoparticles and targeted to CD4+ T cells by surface-attached anti-CD4. In vitro LIF-nano proved efficacious, increasing Foxp3+CD4+ T cell numbers. In vivo, donor-specific Foxp3 Treg expansion was promoted by LIF-nano therapy in recipients of an allogeneic spleen cell transfusion. Confirmation of LIF's involvement in Treg differentiation in vivo was sought by removal of LIF: anti-LIF therapy significantly inhibited antigen-specific nTreg expansion. We conclude that LIF is a Treg cytokine, able to support the Treg lineage and Foxp3 expression during antigen-specific T cell responses. Funding Support: BHF, NIHR, NIH, JDRF, NSFCA.