CD163L1 and CLEC5A discriminate subsets of human resident and inflammatory macrophages in vivo

Macrophages (Mf) can be differentiated and polarized in vitro from human CD14 + monocytes under the influence of GM-CSF (GM-Mf) and M-CSF (M-Mf). GM-Mfs are proinflammatory and M-Mfs have an anti-inflammatory phenotype. We found selective expression of the lectin C-type lectin domain family 5 member A (CLEC5A) transcripts in GM-Mfs and the scavenger receptor CD163 molecule-like 1 (CD163L1) in M-Mfs by microarray assay. In vitro, CD163L1 expression was induced by IL-10 and M-CSF and CLEC5A by inflammatory cytokines and cell adherence. In secondary lymphoid organs, their respective expression was restricted to CD68 + /CD163 + Mfs that preferentially produced either TNF (CLEC5A + ) or IL-10 (CD163L1 + ). Mfs from healthy liver and colon tissue were mostly CD163L1 + , and CLEC5A + cells were scarce. In contrast, CLEC5A + Mfs were abundant in the intestinal lamina propria from patients with inflam- matory bowel disease (IBD), with higher numbers of CLEC5A + CD163L1 + found compared with those in secondary lymphoid organs. CLEC5A + cells were CD14 + CD209 2 CD11b + CD11c + TNF + IL-10 + , and single positive CD163L1 + cells were CD14 2 CD209 + CD11b 2 CD11c 2 TNF 2 IL-10 + in healthy donors and had lost the ability to produce IL-10 and to express CD209 in those with IBD. In melanomas, CLEC5A + tumor-associated Mfs (TAMs) were not detected in 42% of the cases evaluated, but CD163L1 + TAMs were found in 100%. Similar to IBD, CD163L1 + TAMs expressed high levels of CD209 and produced significant amounts of IL-10, and CLEC5A + TAMs were CD14 hi and produced enhanced levels of TNF in metastases. Overall, these results suggest that CD163L1 expres- sion is associated with tissue-resident Mfs with an anti-inflammatory or anergic phenotype and that CLEC5A + Mfs exhibit TNF-producing ability and might display a proinflammatory effect. J. Leukoc. Biol. 98: 000-000; 2015.