Dectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M

Deerhake, M. Elizabeth; Danzaki, Keiko; Inoue, Makoto; Cardakli, Emre D.; Nonaka, Toshiaki; Aggarwal, Nupur; Barclay, William E.; Ji, Ru-Rong; Shinohara, Mari L.

doi:10.1016/j.immuni.2021.01.004

Cited by 48 publications

(51 citation statements)

References 88 publications

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“…CCL4 is a ligand for CCR5, a chemokine receptor on macrophages, microglia, and T cells, and CCR5 was recently shown to be a promising target to ameliorate TBI and stroke suggesting that less of these cells may be beneficial to TBI ( Joy et al, 2019 ). Clec7a is also a marker for the Ccl4 hi TBI microglia, and it plays critical roles in neuroinflammation ( Deerhake et al, 2021 ). Taken together, these pathways and DAM-like microglia may play an important role in TBI and further evaluation is required.…”

Section: Discussionmentioning

confidence: 99%

CCR2 deficiency alters activation of microglia subsets in traumatic brain injury

et al. 2021

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Section: Discussionmentioning

confidence: 99%

CCR2 deficiency alters activation of microglia subsets in traumatic brain injury

et al. 2021

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“…Moreover, the treatment with an anti-galectin-9 antibody led to an exacerbated disease in Wild-Type (WT) compared to Clec7a -/- mice, establishing a positive outcome connection in EAE between galectin-9 and Dectin-1. Thus, Dectin-1 signaling is involved in central nervous system sterile inflammation ( 38 ).…”

Section: Dectin-1 Ligandsmentioning

confidence: 99%

“…However, galectin-9 is not only recognized by T cells but also by myeloid cells. Deerhake E. et al have demonstrated that Dectin-1 signaling in myeloid cells limits neuroinflammation in an experimental autoimmune encephalomyelitis (EAE) model (38). This immunoprotective role is achieved by the production of oncostatin M in neutrophils, a well-established neuroprotective cytokine (51,52).…”

Section: Galectin-9mentioning

confidence: 99%

Dectin-1 Signaling Update: New Perspectives for Trained Immunity

2022

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The C-type lectin receptor Dectin-1 was originally described as the β-glucan receptor expressed in myeloid cells, with crucial functions in antifungal responses. However, over time, different ligands both of microbial-derived and endogenous origin have been shown to be recognized by Dectin-1. The outcomes of this recognition are diverse, including pro-inflammatory responses such as cytokine production, reactive oxygen species generation and phagocytosis. Nonetheless, tolerant responses have been also attributed to Dectin-1, depending on the specific ligand engaged. Dectin-1 recognition of their ligands triggers a plethora of downstream signaling pathways, with complex interrelationships. These signaling routes can be modulated by diverse factors such as phosphatases or tetraspanins, resulting either in pro-inflammatory or regulatory responses. Since its first depiction, Dectin-1 has recently gained a renewed attention due to its role in the induction of trained immunity. This process of long-term memory of innate immune cells can be triggered by β-glucans, and Dectin-1 is crucial for its initiation. The main signaling pathways involved in this process have been described, although the understanding of the above-mentioned complexity in the β-glucan-induced trained immunity is still scarce. In here, we have reviewed and updated all these factors related to the biology of Dectin-1, highlighting the gaps that deserve further research. We believe on the relevance to fully understand how this receptor works, and therefore, how we could harness it in different pathological conditions as diverse as fungal infections, autoimmunity, or cancer.

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“…The current study uncovers additional insights for Dectin-1 signaling during neuroinflammation that diverges from its more well-known signaling pathway via Card9 (Deerhake et al, 2021). Notably in addition to Osm, it appears that Card9-independent Dectin-1 signaling in myeloid cells enriches for transcriptional pathways that include neuroprotective molecules and negative regulators of inflammation.…”

mentioning

confidence: 75%