Peripheral lymph nodes contain migratory and resident innate lymphoid cell populations

Abstract

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.

The Prostaglandin D2 Receptor CRTH2 Promotes IL-33–Induced ILC2 Accumulation in the Lung

“…6C, 6D). These findings suggest that ILC2s can migrate to and also from LNs, an idea that is supported by recent studies that used the Kaede photoconvertible mouse model to provide evidence for the presence of migratory ILC2 in peripheral LNs (79). Taken together, these data (79) and our findings suggest that ILC2s that accumulate in the lung following ongoing i.p.…”

Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19

“…2 ). These serve as the main portal for naive T and B lymphocytes as well as central memory lymphocytes, recirculating neutrophils and ILCs 36 , 37 to enter the draining LNs of the lung and specialized tertiary lymphoid organs along the bronchial tree 38 . The main draining LNs of the lungs are mediastinal LNs, which are positioned along the lower airways (Fig.…”

Metabolic Control of Innate Lymphoid Cell Migration

“…Apart from ILCPs, human blood also contains ILC2s (27), but no mature ILC1s and ILC3s (40). In addition to more abundant NK cells, circulating putative ILCPs and mature ILCs, mainly ILC1s, are also found in mice (42, 43).…”

“…In adult mice, ILCs use similar mechanisms as naïve T cells for lymph node entry (Figure 1). For example, like NK cells, ILCs (especially ILCPs and ILC1s) enter peripheral lymph nodes using CD62L (L-selectin) and CCR7 (42, 43). In addition, LTi-like ILC3s are capable of trafficking from the intestine to draining mesenteric lymph nodes in a CCR7-dependent manner (84).…”