Journal
IMMUNOLOGY
Volume 153, Issue 2, Pages 203-213Publisher
WILEY
DOI: 10.1111/imm.12830
Keywords
myeloid cell; Wnt; monocyte; macrophage; regulation/suppression
Categories
Funding
- National Institutes of Health [5R01NS060632, R01MH00628, R01CA138528]
- CCR, part of NCI's intramural research program, NIH, Department of Health and Human Services (DHHS)
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The variation of macrophage functions suggests the involvement of multiple signalling pathways in fine tuning their differentiation. Macrophages that originate from monocytes in the blood migrate to tissue in response to homeostatic or 'danger' signals and undergo substantial morphological and functional modifications to meet the needs of the dominant signals in the microenvironment. Wnts are secreted glycoproteins that play a significant role in organ and cell differentiation, yet their impact on monocyte differentiation is not clear. In this study, we assessed the role of Wnt1 and Wnt7a on the differentiation of monocytes and the subsequent phenotype and function of monocyte-derived macrophages (MDMs). We show that Wnt7a decreased the expression of CD14, CD11b, CD163 and CD206, whereas Wnt1 had no effect. The Wnt7a effect on CD11b was also observed in the brain and spleen of Wnt7a(-/-) adult brain mouse tissue and in embryonic Wnt7a(-/-) tissue. Wnt7a reduced the phagocytic capacity of M-MDMs, decreased interleukin-10 (IL-10) and IL-12 secretion and increased IL-6 secretion. Collectively, these findings demonstrate that Wnt7a generates an MDM phenotype with both pro-inflammatory and alternative MDM cytokine profiles and reduced phagocytic capacity. As such, Wnt7a can have a significant impact on macrophage responses in health and disease.
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