Differential impact of six JAK inhibitors on myeloid cell differentiation and T cell stimulatory capacity: An in vitro comparative study
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Janus kinase inhibitors (JAKis) modulate immune signaling, yet their effects on myeloid lineages and T-cell responses remain incompletely defined. We systematically compared six JAKis—tofacitinib, baricitinib, peficitinib, upadacitinib, filgotinib, and deucravacitinib—in a GM-CSF/IL-4 bone-marrow culture system. Flow cytometry quantified myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs), DC maturation was assessed by MHC II after LPS, viability by WST-8, and T-cell stimulation by CFSE dilution in co-culture. All JAKis increased MDSCs, while DC differentiation was variably suppressed, most prominently by baricitinib and upadacitinib at lower doses. None of the inhibitors altered MHC II during LPS-induced maturation. Myeloid cells generated with baricitinib or upadacitinib exhibited a markedly reduced capacity to drive T-cell proliferation, whereas tofacitinib, peficitinib, filgotinib, and deucravacitinib showed limited impact. These data indicate that JAK-selectivity governs myeloid composition and downstream T-cell stimulation, with JAK1/2 inhibition exerting the strongest functional effects. Our findings provide a comparative framework for interpreting JAKi immunomodulation and may inform rational selection of agents in immune-mediated diseases.
