ArticleProceedings of the National Academy of Sciences of the United States of America2016
TLR9-mediated inflammation drives a Ccr2-independent peripheral monocytosis through enhanced extramedullary monocytopoiesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
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- In vitro characterization of cellular responses elicited by endosomal TLR agonists encapsulated in Qβ virus-like particles.BMC immunology · 2025Article
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- The Multifaceted Immunology of Cytokine Storm Syndrome.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- IFN-γ is essential for alveolar macrophage-driven pulmonary inflammation in macrophage activation syndrome.JCI insight · 2021Article
- Amelioration of Murine Macrophage Activation Syndrome by Monomethyl Fumarate in Both a Heme Oxygenase 1-Dependent and Heme Oxygenase 1-Independent Manner.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- Electronic Cigarettes Induce Mitochondrial DNA Damage and Trigger TLR9 (Toll-Like Receptor 9)-Mediated Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Diacylglycerol Kinase ζ Regulates Macrophage Responses in Juvenile Arthritis and Cytokine Storm Syndrome Mouse Models.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Mechanisms of action of ruxolitinib in murine models of hemophagocytic lymphohistiocytosis.Blood · 2019Article
- Plcγ2/Tmem178 dependent pathway in myeloid cells modulates the pathogenesis of cytokine storm syndrome.Journal of autoimmunity · 2019Article
- Brief Report: Interferon-γ-Mediated Immunopathology Potentiated by Toll-Like Receptor 9 Activation in a Murine Model of Macrophage Activation Syndrome.Arthritis & rheumatology (Hoboken, N.J.) · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Monocytes are innate immune cells that interact with their environment through the expression of pattern recognition receptors, including Toll-like receptors (TLRs). Both monocytes and TLRs are implicated in driving persistent inflammation in autoimmune diseases. However, cell-intrinsic mechanisms to control inflammation, including TLR tolerance, are thought to limit inflammatory responses in the face of repeated TLR activation, leaving it unclear how chronic TLR-mediated inflammation is maintained in vivo. Herein, we used a well-characterized model of systemic inflammation to determine the mechanisms allowing sustained TLR9 responses to develop in vivo. Monocytes were identified as the main TLR9-responsive cell and accumulated in peripherally inflamed tissues during TLR9-driven inflammation. Intriguingly, canonical mechanisms controlling monocyte production and localization were altered during the systemic inflammatory response, as accumulation of monocytes in the liver and spleen developed in the absence of dramatic increases in bone marrow monocyte progenitors and was independent of chemokine (C-C motif) receptor 2 (Ccr2). Instead, TLR9-driven inflammation induced a Ccr2-independent expansion of functionally enhanced extramedullary myeloid progenitors that correlated with the peripheral accumulation of monocytes in both wild-type and Ccr2(-/-) mice. Our data implicate inflammation-induced extramedullary monocytopoiesis as a peripheral source of newly produced TLR9 responsive monocytes capable of sustaining chronic TLR9 responses in vivo. These findings help to explain how chronic TLR-mediated inflammation may be perpetuated in autoimmune diseases and increase our understanding of how monocytes are produced and positioned during systemic inflammatory responses.
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