Abstract:
:The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the cell subsets that express S1P1 in intestine using S1P1-eGFP mice, the regulation of S1P1 expression in lymphocytes after administration of dextran sulfate sodium (DSS), after colitis induced by transfer of CD4+CD45RBhi cells, and by crossing a mouse with TNF-driven ileitis with S1P1-eGFP mice. We then assayed the expression of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on lymphocyte behavior and S1P1 expression. We found that not only T and B cells express S1P1, but also dendritic (DC) and endothelial cells. Furthermore, chronic but not acute inflammatory signals increased S1P1 expression, while the enzymes that control tissue S1P levels in mice and humans with inflammatory bowel disease (IBD) were uniformly dysregulated, favoring synthesis over degradation. Finally, we observed that FTY720 reduced T-cell velocity and induced S1P1 degradation and retention of Naïve but not effector T cells. Our data demonstrate that chronic inflammation modulates S1P1 expression and tissue S1P levels and suggests that the anti-inflammatory properties of S1PR agonists might not be solely due to their lymphopenic effects, but also due to potential effects on DC migration and vascular barrier function.
journal_name
Mucosal Immunoljournal_title
Mucosal immunologyauthors
Karuppuchamy T,Behrens EH,González-Cabrera P,Sarkisyan G,Gima L,Boyer JD,Bamias G,Jedlicka P,Veny M,Clark D,Peach R,Scott F,Rosen H,Rivera-Nieves Jdoi
10.1038/mi.2016.35subject
Has Abstractpub_date
2017-01-01 00:00:00pages
162-171issue
1eissn
1933-0219issn
1935-3456pii
mi201635journal_volume
10pub_type
杂志文章abstract::This corrects the article DOI: 10.1038/mi.2017.66. ...
journal_title:Mucosal immunology
pub_type: 杂志文章,已发布勘误
doi:10.1038/mi.2017.78
更新日期:2018-03-01 00:00:00
abstract::T helper (Th)1 and Th2 cells play decisive roles in the regulation of resistance vs. susceptibility to pulmonary cryptococcosis. To study the function of interleukin (IL)-4 receptor (IL-4R) on Th cells in pulmonary cryptococcosis, we infected mice specifically lacking IL-4Rα on CD4(+) T cells (Lck(Cre)IL-4Rα(-/lox) mi...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2012.9
更新日期:2012-05-01 00:00:00
abstract::Induction of mucosal immunity is critical for protection from enteric pathogens. Heat shock protein gp96 is one of the primary peptide and protein chaperones located in the endoplasmic reticulum. We reported previously that a cell-secreted gp96-Ig fusion protein (gp96-Ig) mediated strong systemic, antigen-specific CD8...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2009.127
更新日期:2010-03-01 00:00:00
abstract::The mechanism regulating the gastrointestinal epithelial barrier remains poorly understood. We herein demonstrate that Absent in melanoma-2 (AIM2) contributes to the maintenance of intestinal barrier integrity and defense against bacterial infection. AIM2-deficient mice displayed an increased susceptibility to mucosal...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2015.142
更新日期:2016-09-01 00:00:00
abstract::Intranasal inoculation with influenza hemagglutinin subunit with polyinosine-polycytidylic (polyI:C), a synthetic analog for double-stranded RNA, enhances production of vaccine-specific immunoglobulin (Ig) A, which is superior to IgG in prophylactic immunity. The mechanism whereby polyI:C skews to IgA production in th...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2017.48
更新日期:2018-01-01 00:00:00
abstract::Bacterial-induced intestinal inflammation is crucially dependent on interleukin (IL)-23 and is associated with CD4(+) T helper type 1 (Th1) and Th17 responses. However, the relative contributions of these subsets during the induction and resolution of colitis in T-cell-sufficient hosts remain unknown. We report that H...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2013.11
更新日期:2013-11-01 00:00:00
abstract::Specific components of the intestinal microbiota are capable of influencing immune responses such that a mutualistic relationship is established. In mice, colonization with segmented filamentous bacteria (SFB) induces T-helper-17 (Th17) cell differentiation in the intestine, yet the effector functions of interleukin (...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2016.80
更新日期:2017-05-01 00:00:00
abstract::As the Bacillus Calmette-Guérin (BCG) vaccine does not confer long-lasting protection against lung Mycobacterium tuberculosis infection, the development of more efficient vaccines is greatly needed. Here, we used mycobacterial low-molecular weight proteins of the 6-kDa Early Secreted Antigenic Target (ESAT-6) protein ...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2012.92
更新日期:2013-05-01 00:00:00
abstract::Human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infections are believed to infect minimally activated CD4(+) T cells after viral entry. Not much is known about why SIV selectively targets these cells. Here we show that CD4(+) T cells that express high levels of the alpha4beta7 heterodimer are pref...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2009.90
更新日期:2009-09-01 00:00:00
abstract::Cigarette smoke has been associated with susceptibility to different pulmonary and airway diseases. Impaired alveolar macrophages (AMs) that are major phagocytes in the lung have been associated with patients with airway diseases and active smokers. In the current report, we show that exposure to second-hand cigarette...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2015.120
更新日期:2016-07-01 00:00:00
abstract::Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and death worldwide. Immunization with conjugated pneumococcal vaccine has lowered the colonization rate and consequently invasive diseases by inducing serotype-specific antibodies. However, many of the current pneumonia cases...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2016.41
更新日期:2017-01-01 00:00:00
abstract::Nucleotide oligomerization domain (NOD)2 is a member of the NOD-like receptor family of proteins that initiate inflammatory responses when exposed to ligands derived from bacterial components that gain access to the intracellular milieu. It is thus somewhat paradoxical that polymorphisms in the gene that encode NOD2 (...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2008.42
更新日期:2008-11-01 00:00:00
abstract::The tight connection between intestinal inflammation and arthritis in spondyloarthritis (SpA) has been studied extensively. Subclinical gut inflammation, which can be considered as a model for early Crohn's disease, was shown to be strongly associated with joint inflammation. Several early mucosal abnormalities were u...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2008.24
更新日期:2008-09-01 00:00:00
abstract::Periostin is an extracellular matrix protein that has been primarily studied in the context of the heart, where it has been shown to promote cardiac repair and remodeling. In this study, we focused on the role of periostin in an allergic eosinophilic inflammatory disease (eosinophilic esophagitis (EE)) known to involv...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2008.15
更新日期:2008-07-01 00:00:00
abstract::Eosinophils are granulocytes, typically implicated as end-stage effector cells in type-II immune responses. They are capable of producing a wide array of pre-formed molecules which render them with vast potential to influence a wide variety of processes. Nonetheless, eosinophil research has traditionally focused on th...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/s41385-020-0281-y
更新日期:2020-07-01 00:00:00
abstract::Intestinal CD8αα intraepithelial T lymphocytes (T-IELs) have a key role in mucosal immunity and, unlike other T cells, were proposed to differentiate locally. In apparent contradiction, these cells were also shown to originate from a wave of thymus migrants colonizing the gut in the first 3 weeks after birth. We here ...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2010.47
更新日期:2011-01-01 00:00:00
abstract::FoxP3+ regulatory T cells (Tregs) control inflammation and maintain mucosal homeostasis, but their functions during infection are poorly understood. Th1, Th2, and Th17 cells can be identified by master transcription factors (TFs) T-bet, GATA3, and RORγT; Tregs also express these TFs. While T-bet+ Tregs can selectively...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-020-0299-1
更新日期:2020-11-01 00:00:00
abstract::HIV prevention mandates an understanding of the mechanisms of mucosal immunity with attention to some unique features of the epidemic and mucosal environment in the developing world. An effective vaccine will have to induce mucosal protection against a highly diverse virus, which is equipped with a number of immune ev...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2009.23
更新日期:2009-07-01 00:00:00
abstract::De novo differentiation of CD4(+)Foxp3(+) regulatory T cells (induced (i) Tregs) occurs preferentially in the gut-associated lymphoid tissues (GALT). We addressed the contribution of background genetic factors in affecting the balance of iTreg, T helper type 1 (Th1), and Th17 cell differentiation in GALT in vivo follo...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2012.102
更新日期:2013-05-01 00:00:00
abstract::Neutrophils are implicated in the pathogenesis of tuberculosis (TB), a disease caused by Mycobacterium tuberculosis infection, but the mechanisms by which they promote disease are not fully understood. Neutrophils can express cytokines that influence TB progression, and so we compared neutrophil and T-cell expression ...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-019-0195-8
更新日期:2019-11-01 00:00:00
abstract::The ultimate goal for vaccination is to stimulate protective immunological memory. Protection against infectious diseases not only relies on the magnitude of the humoral immune response, but more importantly on the quality and longevity of it. Adjuvants are critical components of most non-living vaccines. Although lit...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/mi.2010.54
更新日期:2010-11-01 00:00:00
abstract::Treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-nuclear factor of activated T cells (NFAT) pathway, including cyclosporine A or tacrolimus, is commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe li...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2016.52
更新日期:2017-03-01 00:00:00
abstract::Cross-presentation of cellular antigens is crucial for priming CD8(+) T cells, and generating immunity to intracellular pathogens--particularly viruses. It is unclear which intestinal phagocytes perform this function in vivo. To address this, we examined dendritic cells (DCs) from the intestinal lymph of IFABP-tOVA 23...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2014.40
更新日期:2015-01-01 00:00:00
abstract::The communities of bacteria that reside in the intestinal tract are in constant competition within this dynamic and densely colonized environment. At homeostasis, the equilibrium that exists between these species and strains is shaped by their metabolism and also by pathways of active antagonism, which drive competiti...
journal_title:Mucosal immunology
pub_type: 杂志文章,评审
doi:10.1038/s41385-018-0053-0
更新日期:2019-01-01 00:00:00
abstract::Intestinal macrophages (mφ) form one of the largest populations of mφ in the body and are vital for the maintenance of gut homeostasis. They have several unique properties and are derived from local differentiation of classical Ly6Chi monocytes, but the factors driving this tissue-specific process are not understood. ...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2016.142
更新日期:2017-11-01 00:00:00
abstract::Whereas gut IgA responses to the microbiota may be multi-centered and diverse, little is known about IgA responses to T-cell-dependent antigens following oral immunizations. Using a novel approach, gut IgA responses to oral hapten (4-hydroxy-3-nitrophenyl)acetyl-cholera toxin (NP-CT) conjugates were followed at the ce...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2012.56
更新日期:2013-01-01 00:00:00
abstract::Lung resident memory CD8 T cells (TRM) are critical for protection against respiratory viruses, but the cellular interactions required for their development are poorly understood. Herein we describe the necessity of classical monocytes for the establishment of lung TRM following influenza infection. We find that, duri...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/s41385-019-0224-7
更新日期:2020-01-01 00:00:00
abstract::The interleukin-23 (IL-23) pathway has emerged as a promising therapeutic target for inflammatory bowel disease. Although the pathogenic role of IL-23 receptor (IL-23R) on T lymphocytes is well established, its function on innate immune cells has not been thoroughly examined. Here we investigate the consequence of IL-...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2011.54
更新日期:2012-01-01 00:00:00
abstract::How the immune system senses aeroallergens and triggers an aberrant inflammation is poorly understood. Dectin-2 is a house dust mite (HDM)-sensing pattern recognition receptor. In a 3-week mouse model of repeated intranasal HDM challenge, anti-Dectin-2 potently attenuated the characteristic allergic inflammation and a...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2013.74
更新日期:2014-05-01 00:00:00
abstract::Interleukin-17 (IL-17)-mediated immunity has emerged as a crucial host defense mechanism against Candida albicans infections in mucosal tissues and the skin. The precise mechanism by which the IL-17 pathway prevents fungal outgrowth has not been clarified. Neutrophils are critical for limiting fungal dissemination and...
journal_title:Mucosal immunology
pub_type: 杂志文章
doi:10.1038/mi.2014.57
更新日期:2015-03-01 00:00:00