Slc6a13 deficiency promotes Th17 responses during intestinal bacterial infection.


:The γ-amino butyric acid (GABA)ergic system shapes the activation and function of immune cells. The present study was conducted to explore the regulation of GABA transporter (GAT)-2 on the differentiation of Th17 cells. Here we found that Th17 cells show higher abundance of GAT-2, and have distinct cellular metabolic signatures, such as the GABA shunt pathway, as compared to naïve T cells. GAT-2 deficiency had little effect on the metabolic signature in naïve T cells, but impaired the GABA uptake and GABA shunt pathway in Th17 cells. GAT-2 deficiency had little effect on T cell development and peripheral T cell homeostasis; however, its deficiency promoted Th17 cell differentiation in vitro. Mechanistically, GAT-2 deficiency promoted differentiation of Th17 cells through activation of GABA-mTOR signaling. In a mouse model of intestinal infection and inflammation, GAT-2 deficiency promoted Th17 responses. Collectively, GAT-2 deficiency promotes Th17 cell responses through activation of GABA-mTOR signaling.


Mucosal Immunol


Mucosal immunology


Ren W,Liao Y,Ding X,Jiang Y,Yan J,Xia Y,Tan B,Lin Z,Duan J,Jia X,Yang G,Deng J,Zhu C,Hardwidge PR,Li J,Zhu G,Yin Y




Has Abstract


2019-03-01 00:00:00














  • Redox signaling regulates commensal-mediated mucosal homeostasis and restitution and requires formyl peptide receptor 1.

    abstract::The mammalian gut microbiota is essential for normal intestinal development, renewal, and repair. Injury to the intestinal mucosa can occur with infection, surgical trauma, and in idiopathic inflammatory bowel disease. Repair of mucosal injury, termed restitution, as well as restoration of intestinal homeostasis invol...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Alam A,Leoni G,Wentworth CC,Kwal JM,Wu H,Ardita CS,Swanson PA,Lambeth JD,Jones RM,Nusrat A,Neish AS

    更新日期:2014-05-01 00:00:00

  • Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection.

    abstract::Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Guo L,Feng K,Wang YC,Mei JJ,Ning RT,Zheng HW,Wang JJ,Worthen GS,Wang X,Song J,Li QH,Liu LD

    更新日期:2017-11-01 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


    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

  • Intravaginal TLR agonists increase local vaccine-specific CD8 T cells and human papillomavirus-associated genital-tumor regression in mice.

    abstract::Human papillomaviruses (HPV)-related cervical cancer is the second leading cause of cancer death in women worldwide. Despite active development, HPV E6/E7 oncogene-specific therapeutic vaccines have had limited clinical efficacy to date. Here, we report that intravaginal (IVAG) instillation of CpG-ODN (TLR9 agonist) o...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Domingos-Pereira S,Decrausaz L,Derré L,Bobst M,Romero P,Schiller JT,Jichlinski P,Nardelli-Haefliger D

    更新日期:2013-03-01 00:00:00

  • Colonic epithelial response to injury requires Myd88 signaling in myeloid cells.

    abstract::Proper colonic injury response requires myeloid-derived cells and Toll-like receptor/Myd88 signaling. However, the precise role of Myd88 signaling specifically in myeloid-derived cells that occurs during tissue damage is unclear. Therefore, we created a mouse line with Myd88 expression restricted to myeloid lineages (...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Malvin NP,Seno H,Stappenbeck TS

    更新日期:2012-03-01 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


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

    更新日期:2011-01-01 00:00:00

  • LRRC31 is induced by IL-13 and regulates kallikrein expression and barrier function in the esophageal epithelium.

    abstract::Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus featuring increased esophageal interleukin-13 (IL-13) levels and impaired barrier function. Herein, we investigated leucine-rich repeat-containing protein 31 (LRRC31) in human EoE esophageal tissue and IL-13-treated esophageal epitheli...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: D'Mello RJ,Caldwell JM,Azouz NP,Wen T,Sherrill JD,Hogan SP,Rothenberg ME

    更新日期:2016-05-01 00:00:00

  • Molecular mechanisms regulating TGF-beta-induced Foxp3 expression.

    abstract::Molecular mechanisms regulating transforming growth factor-beta (TGF-beta) induction of Foxp3 (forkhead box P3) expression and thus induction of induced regulatory T cells (Tregs) have been the focus of a great deal of study in recent years. It has become clear that this process is influenced by a number of factors as...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审


    authors: Xu L,Kitani A,Strober W

    更新日期:2010-05-01 00:00:00

  • Immunization with Ty21a live oral typhoid vaccine elicits crossreactive multifunctional CD8+ T-cell responses against Salmonella enterica serovar Typhi, S. Paratyphi A, and S. Paratyphi B in humans.

    abstract::Previously we have extensively characterized Salmonella enterica serovar Typhi (S. Typhi)-specific cell-mediated immune (CMI) responses in volunteers orally immunized with the licensed Ty21a typhoid vaccine. In this study we measured Salmonella-specific multifunctional (MF) CD8+ T-cell responses to further investigate...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Wahid R,Fresnay S,Levine MM,Sztein MB

    更新日期:2015-11-01 00:00:00

  • Immunoregulatory mechanisms of macrophage PPAR-γ in mice with experimental inflammatory bowel disease.

    abstract::Peroxisome proliferator-activated receptor-γ (PPAR-γ) is widely expressed in macrophages and has been identified as a putative target for the development of novel therapies against inflammatory bowel disease (IBD). Computational simulations identified macrophages as key targets for therapeutic interventions against IB...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Hontecillas R,Horne WT,Climent M,Guri AJ,Evans C,Zhang Y,Sobral BW,Bassaganya-Riera J

    更新日期:2011-05-01 00:00:00

  • Anti-IL-13Rα2 therapy promotes recovery in a murine model of inflammatory bowel disease.

    abstract::There continues to be a major need for more effective inflammatory bowel disease (IBD) therapies. IL-13Rα2 is a decoy receptor that binds the cytokine IL-13 with high affinity and diminishes its STAT6-mediated effector functions. Previously, we found that IL-13Rα2 was necessary for IBD in mice deficient in the anti-in...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Karmele EP,Pasricha TS,Ramalingam TR,Thompson RW,Gieseck RL 3rd,Knilans KJ,Hegen M,Farmer M,Jin F,Kleinman A,Hinds DA,23andMe Research Team.,Almeida Pereira T,de Queiroz Prado R,Bing N,Tchistiakova L,Kasaian MT,Wynn TA

    更新日期:2019-09-01 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


    authors: Jacques P,Elewaut D

    更新日期:2008-09-01 00:00:00

  • Metal-specific CD4+ T-cell responses induced by beryllium exposure in HLA-DP2 transgenic mice.

    abstract::Chronic beryllium disease (CBD) is a granulomatous lung disorder that is associated with the accumulation of beryllium (Be)-specific CD4(+) T cells into the lung. Genetic susceptibility is linked to HLA-DPB1 alleles that possess a glutamic acid at position 69 (βGlu69), and HLA-DPB1*02:01 is the most prevalent βGlu69-c...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Falta MT,Tinega AN,Mack DG,Bowerman NA,Crawford F,Kappler JW,Pinilla C,Fontenot AP

    更新日期:2016-01-01 00:00:00

  • High expression of Sonic hedgehog in allergic airway epithelia contributes to goblet cell metaplasia.

    abstract::Sonic hedgehog (SHH) is abundantly expressed and critical for morphogenesis in embryonic lungs; however, SHH expression drops to a much lower level in mice from E17.5 and in humans from the 21st gestational week. We find that SHH expression is robustly upregulated in the airway epithelia of children with asthma or mou...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Xu C,Zou C,Hussain M,Shi W,Shao Y,Jiang Z,Wu X,Lu M,Wu J,Xie Q,Ke Y,Long F,Tang L,Wu X

    更新日期:2018-09-01 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


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

    更新日期:2016-07-01 00:00:00

  • Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.

    abstract::Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johns...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Fonseca W,Lucey K,Jang S,Fujimura KE,Rasky A,Ting HA,Petersen J,Johnson CC,Boushey HA,Zoratti E,Ownby DR,Levine AM,Bobbit KR,Lynch SV,Lukacs NW

    更新日期:2017-11-01 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


    authors: Lycke N,Bemark M

    更新日期:2010-11-01 00:00:00

  • Mouse and human intestinal immunity: same ballpark, different players; different rules, same score.

    abstract::The study of animal immune physiology and animal models of human disease have accelerated many aspects of translational research by allowing direct, definitive investigations. In particular, the use of mice has allowed genetic manipulation, adoptive transfer, immunization, and focused cell and tissue sampling, which w...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审


    authors: Gibbons DL,Spencer J

    更新日期:2011-03-01 00:00:00

  • Epigallocatechin-3-gallate local pre-exposure application prevents SHIV rectal infection of macaques.

    abstract::Epigallocatechin-3-gallate (EGCG), a natural and major ingredient of green tea, has been shown to have anti-inflammation and anti-HIV-1 properties. We demonstrated that the intrarectal administration of EGCG could protect rhesus macaques from repetitive, intrarectal challenges with low-dose SHIVSF162P3N. This protecti...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Liu JB,Li JL,Zhuang K,Liu H,Wang X,Xiao QH,Li XD,Zhou RH,Zhou L,Ma TC,Zhou W,Liu MQ,Ho WZ

    更新日期:2018-07-01 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


    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

  • Generation of protective pneumococcal-specific nasal resident memory CD4+ T cells via parenteral immunization.

    abstract::The generation of tissue-resident memory T cells (TRM) is an essential aspect of immunity at mucosal surfaces, and it has been suggested that preferential generation of TRM is one of the principal advantages of mucosally administered vaccines. We have previously shown that antigen-specific, IL-17-producing CD4+ T cell...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: O'Hara JM,Redhu NS,Cheung E,Robertson NG,Patik I,Sayed SE,Thompson CM,Herd M,Lucas KB,Conaway E,Morton CC,Farber DL,Malley R,Horwitz BH

    更新日期:2020-01-01 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


    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

  • Retinoic acid takes effector T cells to the gallows: P2X7, the molecular hangman.

    abstract::Effector T-cell contraction is one of the primary means by which immune homeostasis in the peripheral tissues is reestablished following an inflammatory response. In this issue of Mucosal Immunology, Hashimoto-Hill et al.1 show that retinoic acid (RA) transcriptionally upregulates P2X7 primarily in effector T cells of...

    journal_title:Mucosal immunology

    pub_type: 评论,杂志文章


    authors: Das S,Villablanca EJ

    更新日期:2017-07-01 00:00:00

  • The role of miR-155 in cigarette smoke-induced pulmonary inflammation and COPD.

    abstract::Chronic obstructive pulmonary disease (COPD) is a highly prevalent respiratory disease characterized by airflow limitation and chronic inflammation. MiR-155 is described as an ancient regulator of the immune system. Our objective was to establish a role for miR-155 in cigarette smoke (CS)-induced inflammation and COPD...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: De Smet EG,Van Eeckhoutte HP,Avila Cobos F,Blomme E,Verhamme FM,Provoost S,Verleden SE,Venken K,Maes T,Joos GF,Mestdagh P,Brusselle GG,Bracke KR

    更新日期:2020-05-01 00:00:00

  • The reproductive cycle is a pathogenic determinant during gonococcal pelvic inflammatory disease in mice.

    abstract::Women with asymptomatic Neisseria gonorrhoeae infection are at risk of developing pelvic inflammatory disease (PID) if the bacteria ascend from the endocervix into the uterus and oviducts. Factors that affect disease severity, ranging from mild discomfort to severe inflammation, pain, and infertility, remain elusive. ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Islam EA,Shaik-Dasthagirisaheb Y,Kaushic C,Wetzler LM,Gray-Owen SD

    更新日期:2016-07-01 00:00:00

  • Severe viral respiratory infections: are bugs bugging?

    abstract::Viral respiratory tract infections (RTI) pose a high burden on the youngest members of our society. Several risk factors are known for severe viral respiratory disease. However, a large proportion of the severe RTI cannot be explained by these risk factors. A growing body of evidence shows that the composition of the ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审


    authors: Vissers M,de Groot R,Ferwerda G

    更新日期:2014-03-01 00:00:00

  • Single-cell RNA-sequencing identifies the developmental trajectory of C-Myc-dependent NK1.1- T-bet+ intraepithelial lymphocyte precursors.

    abstract::Natural intraepithelial lymphocytes (IELs) are thymus-derived adaptive immune cells, which are important contributors to intestinal immune homeostasis. Similar to other innate-like T cells, they are induced in the thymus through high-avidity interaction that would otherwise lead to clonal deletion in conventional CD4 ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Hummel JF,Zeis P,Ebert K,Fixemer J,Konrad P,Schachtrup C,Arnold SJ,Grün D,Tanriver Y

    更新日期:2020-03-01 00:00:00

  • Targeting the IL-22/IL-22BP axis enhances tight junctions and reduces inflammation during influenza infection.

    abstract::The seasonal burden of influenza coupled with the pandemic outbreaks of more pathogenic strains underscore a critical need to understand the pathophysiology of influenza injury in the lung. Interleukin-22 (IL-22) is a promising cytokine that is critical in protecting the lung during infection. This cytokine is strongl...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Hebert KD,Mclaughlin N,Galeas-Pena M,Zhang Z,Eddens T,Govero A,Pilewski JM,Kolls JK,Pociask DA

    更新日期:2020-01-01 00:00:00

  • Mucosal immunity: aliment and ailments.

    abstract::The development of the primitive gut in the multicellular aquatic eukaryote was driven by the insufficient absorption of nutrients from the oceanic soup. The anatomy of this evolving specialized system invited its colonization by environmental prokaryotes and resulted in the establishment of the intestinal microflora....

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Raz E

    更新日期:2010-01-01 00:00:00

  • The human lung mucosa drives differential Mycobacterium tuberculosis infection outcome in the alveolar epithelium.

    abstract::Mycobacterium tuberculosis (M.tb) is deposited into the alveolus where it first encounters the alveolar lining fluid (ALF) prior contacts host cells. We demonstrated that M.tb-exposure to human ALF alters its cell surface, driving better M.tb infection control by professional phagocytes. Contrary to these findings, ou...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Scordo JM,Olmo-Fontánez AM,Kelley HV,Sidiki S,Arcos J,Akhter A,Wewers MD,Torrelles JB

    更新日期:2019-05-01 00:00:00