Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease

Sutton, Caroline E.; Finlay, Conor M.; Raverdeau, Mathilde; Early, James O.; DeCourcey, Joseph; Zasłona, Zbigniew; O’Neill, Luke A.J.; Mills, Kingston H. G.; Curtis, Anne M.

doi:10.1038/s41467-017-02111-0

Cited by 103 publications

(82 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This temporal immune response in EAE was confirmed in another study where BMAL1 deficiency in myeloid cells (Lyz2-cre:Arntl flox ) also abolished the time-of-day difference in EAE severity of symptoms. Of note, BMAL1-deficient myeloid cells caused a hyperinflammatory environment in the central nervous system through the expansion and infiltration of IL-1b-secreting inflammatory monocytes, which coincided with enhanced severity of EAE relative to control animals [79]. Collectively, these data in mouse models support the cell-autonomous role of BMAL1 in both T cells and myeloid cells in modulating both rhythmic immune cell functions and the severity of autoimmune diseases.…”

Section: Experimental Autoimmune Encephalomyelitismentioning

confidence: 55%

Time-of-Day-Dependent Trafficking and Function of Leukocyte Subsets

Pick¹,

Chen³

et al. 2019

Trends in Immunology

View full text Add to dashboard Cite

show abstract

Section: Experimental Autoimmune Encephalomyelitismentioning

confidence: 55%

Time-of-Day-Dependent Trafficking and Function of Leukocyte Subsets

Pick¹,

Chen³

et al. 2019

Trends in Immunology

View full text Add to dashboard Cite

show abstract

“…4E). While, some recent reports have implicated circadian regulation of the adaptive immune system in disease pathology (20) and lymphocyte trafficking(21), others have not (22). In our model, by day 8 or 10 p.i.…”

Section: Nkt Cells and Nk Cells Are Associated With The Temporal Gatimentioning

confidence: 83%

Circadian control of lung inflammation in influenza infection

Sengupta

Tang

Devine

et al. 2018

Preprint

View full text Add to dashboard Cite

Influenza is a leading cause of respiratory mortality and morbidity. While inflammation is necessary for fighting infection, a fine balance of anti-viral defense and host tolerance is necessary for recovery. Circadian rhythms have been known to modulate inflammation. However, the importance of diurnal variability in the timing of influenza infection is not well understood. Here we demonstrate that endogenous rhythms influence the cellular response to infection in bronchoalveolar lavage (BAL), the pulmonary transcriptomic profile and lesional histology. This time dependent variability does not reflect alterations in viral replication. Rather, we found that better time-dependent outcomes were associated with a preponderance of NK and NKT cells and lower proportion of monocytes in the lung. Thus, host tolerance, rather than viral burden underlies the diurnal gating of influenza induced lung injury. Significance statement:Our work demonstrates the importance of circadian rhythms in influenza infection --a condition with significant public health implications. Our findings, which establish the role of the circadian rhythms in maintaining the balance between host tolerance pathways and anti-viral responses confers a new framework for evaluating the relevance of circadian influences on immunity. \body

show abstract

“…Dendritic cell culture DCs were expanded from bone marrow from naive C57BL/6 mice using GM-CSF as described. 49 Human DCs were generated from PBMCs of healthy donors following a protocol modified from Baleeiro et al 50 Briefly, PBMC derived monocytes were cultured in RPMI with GM-CSF (50 ng/ml) and IL-4 (40 ng/ml) (both Peprotech) for 7 days.…”

Section: T-cell Cytokine Productionmentioning

confidence: 99%

Sustained protective immunity against Bordetella pertussis nasal colonization by intranasal immunization with a vaccine-adjuvant combination that induces IL-17-secreting TRM cells

et al. 2018

Self Cite

View full text Add to dashboard Cite

Current acellular pertussis (aP) vaccines induce strong antibody and Th2 responses but fail to protect against nasal colonization and transmission of Bordetella pertussis. Furthermore, immunity wanes rapidly after immunization. We have developed a novel adjuvant combination (called LP-GMP), comprising c-di-GMP, an intracellular receptor stimulator of interferon genes (STING) agonist, and LP1569, a TLR2 agonist from B. pertussis, which synergistically induces production of IFN-β, IL-12 and IL-23, and maturation of dendritic cells. Parenteral immunization of mice with an experimental aP vaccine formulated with LP-GMP promoted Th1 and Th17 responses and conferred protection against lung infection with B. pertussis. Intranasal immunization with the same aP vaccine-induced potent B. pertussis-specific Th17 responses and IL-17-secreting respiratory tissue-resident memory (T) CD4 T cells, and conferred a high level of protection against nasal colonization as well as lung infection, which was sustained for at least 10 months. Furthermore, long-term protection against nasal colonization with B. pertussis correlated with the number of IL-17-secreting T cells in nasal tissue. Our study has identified an approach for inducing IL-17-secreting T cells that sustain sterilizing immunity against nasal colonization of mice with B. pertussis, and could form the basis of a third generation pertussis vaccine for humans.

show abstract

Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease

Cited by 103 publications

References 44 publications

Time-of-Day-Dependent Trafficking and Function of Leukocyte Subsets

Time-of-Day-Dependent Trafficking and Function of Leukocyte Subsets

Circadian control of lung inflammation in influenza infection

Sustained protective immunity against Bordetella pertussis nasal colonization by intranasal immunization with a vaccine-adjuvant combination that induces IL-17-secreting TRM cells

Contact Info

Product

Resources

About