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1.  Flt3 ligand mediates STAT3-independent expansion, but STAT3-dependent activation of myeloid-derived suppressor cells 
The Flt3-Flt3 ligand (Flt3L) pathway is critically involved in the differentiation and homeostasis of myeloid cells, including dendritic cells (DC); however, its role in the expansion and function of myeloid-derived suppressor cells (MDSC) has not been determined. Herein, we describe the ability of Flt3L to expand and activate murine MDSC capable of suppressing allograft rejection upon adoptive transfer. While Flt3L expands and augments the stimulatory capacity of myeloid DC, MDSC expanded by Flt3L have increased suppressive activity. Although STAT3 is considered the central transcription factor for MDSC expansion, inhibition and genetic ablation of STAT3 did not block, but augmented Flt3L-mediated MDSC expansion. MDSC suppressive function, preserved when STAT3 inhibition was removed, was reduced by genetic STAT3 deletion. Both STAT3 inhibition and deletion reduced Flt3L-mediated DC expansion, signifying that STAT3 had reciprocal effects on suppressive MDSC and immunostimulatory DC expansion. Together, these findings enhance understanding of the immunomodulatory properties of Flt3L.
doi:10.4049/jimmunol.1300058
PMCID: PMC3994403  PMID: 24639346
2.  Regulatory Myeloid Cells in Transplantation 
Transplantation  2014;97(4):367-379.
Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages (Mreg), regulatory dendritic cells (DCreg) and myeloid-derived suppressor cells (MDSC) to regulate alloimmunity, their potential as cellular therapeutic agents and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity following RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and usher in a new era of immune modulation exploiting cells of myeloid origin.
doi:10.1097/TP.0b013e3182a860de
PMCID: PMC3944083  PMID: 24092382
immune regulation; myeloid cells; transplantation
3.  Regulatory role of vitamin D in T-cell reactivity against myelin peptides in relapsing-remitting multiple sclerosis patients 
BMC Neurology  2012;12:103.
Background
Low levels of plasma 25-hydroxyvitaminD (25(OH)D) are associated with a higher incidence of multiple sclerosis (MS) due to the immune suppressive properties of vitamin D.
The aim of this study was to determine the correlation between plasma 25(OH)D concentrations and clinical and immunological variables in a cohort of multiple sclerosis patients.
Methods
Plasma 25(OH)D concentrations were evaluated in summer and winter in 15 primary progressive MS (PPMS) patients, 40 relapsing- remitting MS (RRMS) patients and 40 controls (HC). Protocol variables included demographic and clinical data, radiological findings and immunological variables (oligoclonal bands, HLADR15 and T-lymphocyte proliferation to a definite mix of 7 myelin peptides).
Results
During the winter, plasma concentrations were significantly lower in RRMS patients compared to HC, whereas no differences were found in summer. No relationships were found between plasma 25(OH)D concentrations and clinical or radiological variables. RRMS patients with a positive T-cell proliferation to a mix of myelin peptides (n = 31) had lower 25(OH)D concentrations.
Conclusions
25(OH)D is an immunomodulatory molecule that might have a regulatory role in T-cell proliferation to myelin peptides in RRMS patients.
doi:10.1186/1471-2377-12-103
PMCID: PMC3488583  PMID: 23006125
Multiple sclerosis; T-cell proliferation; Vitamin D

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