Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease.

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 Immunol

journal_title

Mucosal immunology

authors

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 J

doi

10.1038/mi.2016.35

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

162-171

issue

1

eissn

1933-0219

issn

1935-3456

pii

mi201635

journal_volume

10

pub_type

杂志文章
  • Campylobacter jejuni impairs sodium transport and epithelial barrier function via cytokine release in human colon.

    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

    authors: Bücker R,Krug SM,Moos V,Bojarski C,Schweiger MR,Kerick M,Fromm A,Janßen S,Fromm M,Hering NA,Siegmund B,Schneider T,Barmeyer C,Schulzke JD

    更新日期:2018-03-01 00:00:00

  • Lack of IL-4 receptor expression on T helper cells reduces T helper 2 cell polyfunctionality and confers resistance in allergic bronchopulmonary mycosis.

    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

    authors: Müller U,Piehler D,Stenzel W,Köhler G,Frey O,Held J,Grahnert A,Richter T,Eschke M,Kamradt T,Brombacher F,Alber G

    更新日期:2012-05-01 00:00:00

  • Cell-secreted Gp96-Ig-peptide complexes induce lamina propria and intraepithelial CD8+ cytotoxic T lymphocytes in the intestinal mucosa.

    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

    authors: Strbo N,Pahwa S,Kolber MA,Gonzalez L,Fisher E,Podack ER

    更新日期:2010-03-01 00:00:00

  • AIM2 contributes to the maintenance of intestinal integrity via Akt and protects against Salmonella mucosal infection.

    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

    authors: Hu GQ,Song PX,Li N,Chen W,Lei QQ,Yu SX,Zhang XJ,Du CT,Deng XM,Han WY,Yang YJ

    更新日期:2016-09-01 00:00:00

  • Toll-like receptor 3 in nasal CD103+ dendritic cells is involved in immunoglobulin A production.

    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

    authors: Takaki H,Kure S,Oshiumi H,Sakoda Y,Suzuki T,Ainai A,Hasegawa H,Matsumoto M,Seya T

    更新日期:2018-01-01 00:00:00

  • Th17-cell plasticity in Helicobacter hepaticus-induced intestinal inflammation.

    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

    authors: Morrison PJ,Bending D,Fouser LA,Wright JF,Stockinger B,Cooke A,Kullberg MC

    更新日期:2013-11-01 00:00:00

  • IL-17A-mediated neutrophil recruitment limits expansion of segmented filamentous bacteria.

    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

    authors: Flannigan KL,Ngo VL,Geem D,Harusato A,Hirota SA,Parkos CA,Lukacs NW,Nusrat A,Gaboriau-Routhiau V,Cerf-Bensussan N,Gewirtz AT,Denning TL

    更新日期:2017-05-01 00:00:00

  • Induction of protective immunity against Mycobacterium tuberculosis by delivery of ESX antigens into airway dendritic cells.

    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

    authors: Dong H,Stanek O,Salvador FR,Länger U,Morillon E,Ung C,Sebo P,Leclerc C,Majlessi L

    更新日期:2013-05-01 00:00:00

  • Alpha4(+)beta7(hi)CD4(+) memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection.

    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

    authors: Kader M,Wang X,Piatak M,Lifson J,Roederer M,Veazey R,Mattapallil JJ

    更新日期:2009-09-01 00:00:00

  • Restoring cigarette smoke-induced impairment of efferocytosis in alveolar macrophages.

    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

    authors: Subramaniam R,Mukherjee S,Chen H,Keshava S,Neuenschwander P,Shams H

    更新日期:2016-07-01 00:00:00

  • Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection.

    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

    authors: Wang Y,Jiang B,Guo Y,Li W,Tian Y,Sonnenberg GF,Weiser JN,Ni X,Shen H

    更新日期:2017-01-01 00:00:00

  • The molecular basis of NOD2 susceptibility mutations in Crohn's disease.

    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

    authors: Strober W,Kitani A,Fuss I,Asano N,Watanabe T

    更新日期:2008-11-01 00:00:00

  • Joint expedition: linking gut inflammation to arthritis.

    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

    authors: Jacques P,Elewaut D

    更新日期:2008-09-01 00:00:00

  • Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses.

    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

    authors: Blanchard C,Mingler MK,McBride M,Putnam PE,Collins MH,Chang G,Stringer K,Abonia JP,Molkentin JD,Rothenberg ME

    更新日期:2008-07-01 00:00:00

  • The emerging roles of eosinophils in mucosal homeostasis.

    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

    authors: Shah K,Ignacio A,McCoy KD,Harris NL

    更新日期:2020-07-01 00:00:00

  • The role of the gut as a primary lymphoid organ: CD8αα intraepithelial T lymphocytes in euthymic mice derive from very immature CD44+ thymocyte precursors.

    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

    authors: Peaudecerf L,dos Santos PR,Boudil A,Ezine S,Pardigon N,Rocha B

    更新日期:2011-01-01 00:00:00

  • Regulatory T cells control the dynamic and site-specific polarization of total CD4 T cells following Salmonella infection.

    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

    authors: Clay SL,Bravo-Blas A,Wall DM,MacLeod MKL,Milling SWF

    更新日期:2020-11-01 00:00:00

  • An African perspective on mucosal immunity and HIV-1.

    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

    authors: Pala P,Gomez-Roman VR,Gilmour J,Kaleebu P

    更新日期:2009-07-01 00:00:00

  • Host-dependent control of early regulatory and effector T-cell differentiation underlies the genetic susceptibility of RAG2-deficient mouse strains to transfer colitis.

    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

    authors: Valatas V,He J,Rivollier A,Kolios G,Kitamura K,Kelsall BL

    更新日期:2013-05-01 00:00:00

  • Neutrophils express pro- and anti-inflammatory cytokines in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques.

    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

    authors: Gideon HP,Phuah J,Junecko BA,Mattila JT

    更新日期:2019-11-01 00:00:00

  • Mucosal adjuvants and long-term memory development with special focus on CTA1-DD and other ADP-ribosylating toxins.

    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

    authors: Lycke N,Bemark M

    更新日期:2010-11-01 00:00:00

  • Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis.

    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

    authors: Zelante T,Wong AY,Mencarelli A,Foo S,Zolezzi F,Lee B,Poidinger M,Ricciardi-Castagnoli P,Fric J

    更新日期:2017-03-01 00:00:00

  • Lymph-borne CD8α+ dendritic cells are uniquely able to cross-prime CD8+ T cells with antigen acquired from intestinal epithelial cells.

    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

    authors: Cerovic V,Houston SA,Westlund J,Utriainen L,Davison ES,Scott CL,Bain CC,Joeris T,Agace WW,Kroczek RA,Mowat AM,Yrlid U,Milling SW

    更新日期:2015-01-01 00:00:00

  • Interbacterial mechanisms of colonization resistance and the strategies pathogens use to overcome them.

    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

    authors: Sorbara MT,Pamer EG

    更新日期:2019-01-01 00:00:00

  • Tissue-specific differentiation of colonic macrophages requires TGFβ receptor-mediated signaling.

    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

    authors: Schridde A,Bain CC,Mayer JU,Montgomery J,Pollet E,Denecke B,Milling SWF,Jenkins SJ,Dalod M,Henri S,Malissen B,Pabst O,Mcl Mowat A

    更新日期:2017-11-01 00:00:00

  • Re-utilization of germinal centers in multiple Peyer's patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses.

    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

    authors: Bergqvist P,Stensson A,Hazanov L,Holmberg A,Mattsson J,Mehr R,Bemark M,Lycke NY

    更新日期:2013-01-01 00:00:00

  • Pulmonary monocytes interact with effector T cells in the lung tissue to drive TRM differentiation following viral infection.

    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

    authors: Dunbar PR,Cartwright EK,Wein AN,Tsukamoto T,Tiger Li ZR,Kumar N,Uddbäck IE,Hayward SL,Ueha S,Takamura S,Kohlmeier JE

    更新日期:2020-01-01 00:00:00

  • Opposing consequences of IL-23 signaling mediated by innate and adaptive cells in chemically induced colitis in mice.

    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

    authors: Cox JH,Kljavin NM,Ota N,Leonard J,Roose-Girma M,Diehl L,Ouyang W,Ghilardi N

    更新日期:2012-01-01 00:00:00

  • Dectin-2 sensing of house dust mite is critical for the initiation of airway inflammation.

    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

    authors: Clarke DL,Davis NH,Campion CL,Foster ML,Heasman SC,Lewis AR,Anderson IK,Corkill DJ,Sleeman MA,May RD,Robinson MJ

    更新日期:2014-05-01 00:00:00

  • IL-17-mediated antifungal defense in the oral mucosa is independent of neutrophils.

    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

    authors: Trautwein-Weidner K,Gladiator A,Nur S,Diethelm P,LeibundGut-Landmann S

    更新日期:2015-03-01 00:00:00