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IL-7 is a key regulator of naïve T cell homeostasis including T cell development, survival, and proliferation. IL-7 is highly expressed in lymph nodes (LNs), and we investigated the potential for IL-7 to drive naïve T cell movement in LNs. We show that IL-7 can mediate high speed T cell movement in vitro and in LNs. Downstream of IL-7R, T cell motility requires JAK1/3 and STAT5 activation, but mTOR signaling is not required. Using computational modeling and imaging of T cell motion in lymph nodes through two photon microscopy, we find that IL-7R-mediated motility accounts for T cell localization near DCs in the LN, suggesting that IL-7 can regulate naive T cell contacts with DCs. These data demonstrate a novel role for the IL-7/IL-7R pathway in controlling rapid T cell motility, showing that IL-7/IL-7R mediated T cell motion can facilitate efficient T cell-DC interactions in the LN. • We show a novel role for IL-7 in driving high speed T cell motility in lymph nodes. • T cell motility downstream of IL-7R requires JAK/STAT signaling and RhoA, but interestingly, not mTOR. • IL-7R signaling mediates T cell contact with DCs, but does not enable T cells moving chemotactically towards DCs.
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Byrum et al. (2025) studied this question.
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