Peripheral lymph nodes contain migratory and resident innate lymphoid cell populations

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Science Immunology  31 May 2019:
Vol. 4, Issue 35, eaau8082
DOI: 10.1126/sciimmunol.aau8082

Innate drifters

Innate lymphoid cells (ILCs) are regarded as tissue-resident sentries that stay put in peripheral tissues or lymphoid organs rather than extensively recirculating like most B and T cells. Dutton et al. used direct illumination to mark all cells in a single peripheral lymph node of transgenic mice expressing a photoconvertible fluorescent reporter protein. Migration versus continuing residence of the marked cells was monitored by flow cytometry. This experimental approach showed that ILC1s in a lymph node have more propensity to migrate away from that lymph node than ILC2s and ILC3s but still considerably less than T cells. The findings from this study reveal that some ILC subsets are not exclusively sessile and routinely traffic between different anatomic sites while carrying out their immunosurveillance mission.


Tissue residency is considered a defining feature of the innate lymphoid cell (ILC) populations located within mucosal and adipose tissues. ILCs are also present within all lymphoid tissues, but whether ILCs migrate between lymphoid and nonlymphoid sites and in what context is poorly understood. To determine whether migratory ILCs exist within peripheral lymph nodes (LNs), we labeled all cells within the brachial LN (bLN) of transgenic mice expressing a photoconvertible fluorescent protein by direct exposure to light. Tracking of cellular changes in the labeled LN revealed the gradual migration of new ILCs into the tissue, balanced by egress of ILCs dependent on sphingosine-1-phosphate receptors. Most of the migratory ILCs were ILC1s, entering LNs directly from the circulation in a CD62L- and CCR7-dependent manner and thus behaving like conventional natural killer (cNK) cells. Upon egress, both ILC1s and cNK cells were found to recirculate through peripheral LNs. A distinct population of migratory ILC2s were detected in the LN, but most of the ILC3s were tissue resident. Functionally, both migratory and resident ILC1s within LNs were able to rapidly produce IFN-γ to support the generation of robust TH1 T cell responses after immunization. Thus, migratory and resident ILC populations exist within peripheral LNs, with ILC1s, akin to cNK cells, able to traffic into these tissues where they can contribute to the initiation of adaptive immunity.

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