InVivoMAb anti-mouse LPAM-1 (Integrin α4β7)
Product Details
The DATK32 monoclonal antibody reacts with mouse LPAM-1 also known as integrin alpha 4 beta 7. The 130 kDa integrin β7 chain associates with the 150 kDa integrin α4 (CD49d) chain to form LPAM-1, a member of the Ig superfamily. LPAM-1 is expressed by peripheral lymphocytes, small subsets of thymocytes, and bone marrow progenitors. LPAM-1 binds VCAM-1 (CD106), MAdCAM-1, and fibronectin and facilitates lymphocyte adhesion and migration to the intestine and associated lymphoid tissues. The DATK32 antibody has been reported to block LPAM-1-mediated cell adhesion in vivo.Specifications
| Isotype | Rat IgG2a, κ |
|---|---|
| Recommended Isotype Control(s) | InVivoMAb rat IgG2a isotype control, anti-trinitrophenol |
| Recommended Dilution Buffer | InVivoPure pH 7.0 Dilution Buffer |
| Conjugation | This product is unconjugated. Conjugation is available via our Antibody Conjugation Services. |
| Immunogen | TK1 cells |
| Reported Applications |
in vivo Integrin α4β7 neutralization Flow cytometry |
| Formulation |
PBS, pH 7.0 Contains no stabilizers or preservatives |
| Endotoxin |
<2EU/mg (<0.002EU/μg) Determined by LAL gel clotting assay |
| Purity |
>95% Determined by SDS-PAGE |
| Sterility | 0.2 µm filtration |
| Production | Purified from cell culture supernatant in an animal-free facility |
| Purification | Protein G |
| RRID | AB_1107713 |
| Molecular Weight | 150 kDa |
| Storage | The antibody solution should be stored at the stock concentration at 4°C. Do not freeze. |
Recommended Products
-
Recommended Isotype Control(s)
InVivoMAb rat IgG2a isotype control, anti-trinitrophenol
-
Recommended Dilution Buffer
InVivoPure pH 7.0 Dilution Buffer
in vivo Integrin α4β7 neutralization
Duc, D., et al. (2019). "Disrupting Myelin-Specific Th17 Cell Gut Homing Confers Protection in an Adoptive Transfer Experimental Autoimmune Encephalomyelitis" Cell Rep 29(2): 378-390.e374. PubMed
Multiple sclerosis (MS) is a common autoimmune disease of the CNS. Although an association between MS and inflammatory bowel diseases is observed, the link connecting intestinal immune responses and neuroinflammation remains unclear. Here we show that encephalitogenic Th17 cells infiltrate the colonic lamina propria before neurological symptom development in two murine MS models, active and adoptive transfer experimental autoimmune encephalomyelitis (EAE). Specifically targeting Th17 cell intestinal homing by blocking the α4β7-integrin and its ligand MAdCAM-1 pathway impairs T cell migration to the large intestine and dampens EAE severity in the Th17 cell adoptive transfer model. Mechanistically, myelin-specific Th17 cells proliferate in the colon and affect gut microbiota composition. The beneficial effect of blocking the α4β7-integrin and its ligand MAdCAM-1 pathway on EAE is interdependent with gut microbiota. Those results show that disrupting myelin-specific Th17 cell trafficking to the large intestine harnesses neuroinflammation and suggests that the gut environment and microbiota catalyze the encephalitogenic properties of Th17 cells.
in vivo Integrin α4β7 neutralization
Bemark, M., et al. (2016). "Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization" Nat Commun 7: 12698. PubMed
Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8(high)/GFP(+) NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured. They are α4β7-integrin(+)CD73(+)PD-L2(+)CD80(+) and at systemic sites mostly IgM(+), while 80% are IgA(+) in Peyer’s patches. On reactivation, most memory B cells in Peyer’s patches are GL7(-), but expand in germinal centres and acquire higher affinity and more mutations, demonstrating strong clonal selection. CCR9 expression is found only in Peyer’s patches and appears critical for gut homing. Thus, gut mucosal memory possesses unique features not seen after systemic immunization.
in vivo Integrin α4β7 neutralization
Sheridan, B. S., et al. (2014). "Oral infection drives a distinct population of intestinal resident memory CD8(+) T cells with enhanced protective function" Immunity 40(5): 747-757. PubMed
The intestinal mucosa promotes T cell responses that might be beneficial for effective mucosal vaccines. However, intestinal resident memory T (Trm) cell formation and function are poorly understood. We found that oral infection with Listeria monocytogenes induced a robust intestinal CD8 T cell response and blocking effector T cell migration showed that intestinal Trm cells were critical for secondary protection. Intestinal effector CD8 T cells were predominately composed of memory precursor effector cells (MPECs) that rapidly upregulated CD103, which was needed for T cell accumulation in the intestinal epithelium. CD103 expression, rapid MPEC formation, and maintenance in intestinal tissues were dependent on T cell intrinsic transforming growth factor beta signals. Moreover, intestinal Trm cells generated after intranasal or intravenous infection were less robust and phenotypically distinct from Trm cells generated after oral infection, demonstrating the critical contribution of infection route for directing the generation of protective intestinal Trm cells.
in vivo Integrin α4β7 neutralization, Flow Cytometry
Rosser, E. C., et al. (2014). "Regulatory B cells are induced by gut microbiota-driven interleukin-1beta and interleukin-6 production" Nat Med 20(11): 1334-1339. PubMed
Regulatory B cells (Breg cells) differentiate in response to inflammation and subsequently restrain excessive immune responses via the release of interleukin-10 (IL-10). However, the precise inflammatory signals governing their differentiation remain to be elucidated. Here we show that the gut microbiota promotes the differentiation of Breg cells in the spleen as well as in the mesenteric lymph nodes. Perturbation of the gut microbiome imposed either by antibiotic treatment or by changes in the sterility of housing conditions reduces the number and function of Breg cells. Following the induction of arthritis, IL-1beta and IL-6 are produced only in conventionally housed mice and both cytokines directly promote Breg cell differentiation and IL-10 production. Mice lacking IL-6 receptor (IL-6R) or IL-1 receptor 1 (IL-1R1) specifically on B cells have a reduced number of IL-10-producing B cells and develop exacerbated arthritis compared to control animals. Thus, in response to inflammatory signals induced by both the gut flora and arthritis, Breg cells increase in number and restrain excessive inflammation.
in vivo Integrin α4β7 neutralization
Lindebo Holm, T., et al. (2012). "Pharmacological Evaluation of the SCID T Cell Transfer Model of Colitis: As a Model of Crohn’s Disease" Int J Inflam 2012: 412178. PubMed
Animal models are important tools in the development of new drug candidates against the inflammatory bowel diseases (IBDs) Crohn’s disease and ulcerative colitis. In order to increase the translational value of these models, it is important to increase knowledge relating to standard drugs. Using the SCID adoptive transfer colitis model, we have evaluated the effect of currently used IBD drugs and IBD drug candidates, that is, anti-TNF-alpha, TNFR-Fc, anti-IL-12p40, anti-IL-6, CTLA4-Ig, anti-alpha4beta7 integrin, enrofloxacin/metronidazole, and cyclosporine. We found that anti-TNF-alpha, antibiotics, anti-IL-12p40, anti-alpha4beta7 integrin, CTLA4-Ig, and anti-IL-6 effectively prevented onset of colitis, whereas TNFR-Fc and cyclosporine did not. In intervention studies, antibiotics, anti-IL-12p40, and CTLA4-Ig induced remission, whereas the other compounds did not. The data suggest that the adoptive transfer model and the inflammatory bowel diseases have some main inflammatory pathways in common. The finding that some well-established IBD therapeutics do not have any effect in the model highlights important differences between the experimental model and the human disease.
- Mus musculus (House mouse),
- Immunology and Microbiology
Overcoming Resistance to Immune Checkpoint Inhibitor Therapy Using Calreticulin-Inducing Nanoparticle.
In Pharmaceutics on 9 June 2023 by Chandrasekar, S. V., Singh, A., et al.
PubMed
Nanoparticles (NPs) have the ability to transform poorly immunogenic tumors into activated 'hot' targets. In this study, we investigated the potential of a liposome-based nanoparticle (CRT-NP) expressing calreticulin as an in-situ vaccine to restore sensitivity to anti-CTLA4 immune checkpoint inhibitor (ICI) in CT26 colon tumors. We found that a CRT-NP with a hydrodynamic diameter of approximately 300 nm and a zeta potential of approximately +20 mV induced immunogenic cell death (ICD) in CT-26 cells in a dose-dependent manner. In the mouse model of CT26 xenograft tumors, both CRT-NP and ICI monotherapy caused moderate reductions in tumor growth compared to the untreated control group. However, the combination therapy of CRT-NP and anti-CTLA4 ICI resulted in remarkable suppression of tumor growth rates (>70%) compared to untreated mice. This combination therapy also reshaped the tumor microenvironment (TME), achieving the increased infiltration of antigen-presenting cells (APCs) such as dendritic cells and M1 macrophages, as well as an abundance of T cells expressing granzyme B and a reduction in the population of CD4+ Foxp3 regulatory cells. Our findings indicate that CRT-NPs can effectively reverse immune resistance to anti-CTLA4 ICI therapy in mice, thereby improving the immunotherapeutic outcome in the mouse model.
- Cancer Research,
- Immunology and Microbiology
The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer.
In Cellular and Molecular Gastroenterology and Hepatology on 5 November 2022 by Collard, M. K., Tourneur-Marsille, J., et al.
PubMed
Although appendectomy may reduce colorectal inflammation in patients with ulcerative colitis (UC), this surgical procedure has been suggested to be associated with an increased risk of colitis-associated cancer (CAC). Our aim was to explore the mechanism underlying the appendectomy-associated increased risk of CAC. Five-week-old male BALB/c mice underwent appendectomy, appendicitis induction, or sham laparotomy. They were then exposed to azoxymethane/dextran sodium sulfate (AOM/DSS) to induce CAC. Mice were killed 12 weeks later, and colons were taken for pathological analysis and immunohistochemistry (CD3 and CD8 staining). Human colonic tumors from 21 patients with UC who underwent surgical resection for CAC were immunophenotyped and stratified according to appendectomy status. Whereas appendectomy significantly reduced colitis severity and increased CAC number, appendicitis induction without appendectomy led to opposite results. Intratumor CD3+ and CD8+ T-cell densities were lower after appendectomy and higher after appendicitis induction compared with the sham laparotomy group. Blocking lymphocyte trafficking to the colon with the anti-α4β7 integrin antibody or a sphingosine-1-phosphate receptor agonist suppressed the inducing effect of the appendectomy on tumors' number and on CD3+/CD8+ intratumoral density. CD8+ or CD3+ T cells isolated from inflammatory neo-appendix and intravenously injected into AOM/DSS-treated recipient mice increased CD3+/CD8+ T-cell tumor infiltration and decreased tumor number. In UC patients with a history of appendectomy, intratumor CD3+ and CD8+ T-cell densities were decreased compared with UC patients without history of appendectomy. In UC, appendectomy could suppress a major site of T-cell priming, resulting in a less efficient CAC immunosurveillance. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
- Immu-depl,
- In Vivo,
- Mus musculus (House mouse),
- Immunology and Microbiology
Recruitment of α4β7 monocytes and neutrophils to the brain in experimental colitis is associated with elevated cytokines and anxiety-like behavior.
In Journal of Neuroinflammation on 4 April 2022 by Cluny, N. L., Nyuyki, K. D., et al.
PubMed
Behavioral comorbidities, such as anxiety and depression, are a prominent feature of IBD. The signals from the inflamed gut that cause changes in the brain leading to these behavioral comorbidities remain to be fully elucidated. We tested the hypothesis that enhanced leukocyte-cerebral endothelial cell interactions occur in the brain in experimental colitis, mediated by α4β7 integrin, to initiate neuroimmune activation and anxiety-like behavior. Female mice treated with dextran sodium sulfate were studied at the peak of acute colitis. Circulating leukocyte populations were determined using flow cytometry. Leukocyte-cerebral endothelial cell interactions were examined using intravital microscopy in mice treated with anti-integrin antibodies. Brain cytokine and chemokines were assessed using a multiplex assay in animals treated with anti-α4β7 integrin. Anxiety-like behavior was assessed using an elevated plus maze in animals after treatment with an intracerebroventricular injection of interleukin 1 receptor antagonist. The proportion of classical monocytes expressing α4β7 integrin was increased in peripheral blood of mice with colitis. An increase in the number of rolling and adherent leukocytes on cerebral endothelial cells was observed, the majority of which were neutrophils. Treatment with anti-α4β7 integrin significantly reduced the number of rolling leukocytes. After anti-Ly6C treatment to deplete monocytes, the number of rolling and adhering neutrophils was significantly reduced in mice with colitis. Interleukin-1β and CCL2 levels were elevated in the brain and treatment with anti-α4β7 significantly reduced them. Enhanced anxiety-like behavior in mice with colitis was reversed by treatment with interleukin 1 receptor antagonist. In experimental colitis, α4β7 integrin-expressing monocytes direct the recruitment of neutrophils to the cerebral vasculature, leading to elevated cytokine levels. Increased interleukin-1β mediates anxiety-like behavior. © 2022. The Author(s).
- Neuroscience
Leukocyte - Cerebral Endothelial Cell Interactions in the Brain Lead to Anxiety-like Behaviour in Experimental Colitis
Preprint on Research Square on 3 December 2021 by Cluny, N. L., Nyuyki, K. D., et al.
PubMed
BACKGROUND Behavioral comorbidities, such as anxiety and depression, are a prominent feature of IBD. The signals from the inflamed gut that cause changes in the brain leading to these behavioral comorbidities remain to be fully elucidated. We tested the hypothesis that enhanced leukocyte - cerebral endothelial cell interactions in experimental colitis initiate neuroimmune activation leading to anxiety-like behaviour. METHODS Male and female mice treated with dextran sodium sulfate were studied at the peak of acute colitis. Circulating leukocyte populations were determined using flow cytometry. Leukocyte - cerebral endothelial cell interactions were examined using intravital microscopy in mice treated with anti-integrin antibodies. Brain cytokine and chemokines were assessed using a multiplex assay in animals treated with anti-α4β7 integrin. Anxiety-like behavior was assessed using an elevated plus maze in animals after treatment with an intracerebroventricular injection of interleukin 1 receptor antagonist. RESULTS The proportion of classical monocytes expressing α4β7 integrin was increased in peripheral blood of mice with colitis. An increase in the number of rolling and adherent leukocytes on cerebral endothelial cells was observed, the majority of which were neutrophils. Treatment with anti-α4β7 integrin significantly reduced the number of rolling leukocytes. After anti-Ly6C treatment to deplete monocytes, the number of rolling and adhering neutrophils were significantly reduced in mice with colitis. Interleukin-1β levels were elevated in the brain and treatment with anti-α4β7 significantly reduced them. Enhanced anxiety-like behaviour in mice with colitis was reversed by treatment with interleukin 1 receptor antagonist. CONCLUSIONS α4β7 integrin expressing monocytes direct the recruitment of neutrophils to the brain vasculature, leading to elevated cytokine levels that mediate anxiety-like behaviour in experimental colitis.
- Mus musculus (House mouse),
- Cancer Research,
- Immunology and Microbiology
The appendix orchestrates T-cell mediated immunosurveillance in colitis-associated cancer
Preprint on MedRxiv : the Preprint Server for Health Sciences on 27 May 2021 by Collard, M. K., Tourneur-Marsille, J., et al.
PubMed
h4>Objective/h4> While appendectomy may reduce colorectal inflammation in patients with ulcerative colitis (UC), appendectomy has been suggested to be associated with an increased risk of colitis-associated cancer (CAC). The aim of this study was to explore the mechanism underlying the appendectomy-associated increased risk of CAC. h4>Design/h4> Five-week-old male BALB/c mice underwent appendectomy, appendicitis induction or sham laparotomy. They were then exposed to azoxymethane/dextran sodium sulfate (AOM/DSS) to induce CAC. Mice were sacrificed 12 weeks later, and colons were taken for pathological analysis and immunohistochemistry (CD3 and CD8 staining). Human colonic tumors from 21 UC patients who underwent surgical resection for CAC were immunophenotyped and stratified according to the appendectomy status. h4>Results/h4> While appendectomy significantly reduced colitis severity and increased CAC number, appendicitis induction without appendectomy led to opposite results. Intra-tumor CD3+ and CD8+ T-cell densities were lower after appendectomy and higher after appendicitis induction compared to the sham laparotomy group. Blocking lymphocyte trafficking to the colon with the anti-α4β7 integrin antibody or a sphingosine-1-phosphate receptor agonist suppressed the inducing effect of the appendectomy on tumors’ number and on CD3+/CD8+ intra-tumoral density. CD8+ or CD3+ T cells isolated from inflammatory neo-appendix and intravenously injected into AOM/DSS-treated recipient mice increased CD3+/CD8+ T-cell tumor infiltration and decreased tumor number. In UC patients with a history of appendectomy, intra-tumor CD3+ and CD8+ T-cell densities were decreased compared to UC patients without history of appendectomy. h4>Conclusions/h4> In UC, appendectomy could suppress a major site of T-cell priming resulting in a less efficient CAC immunosurveillance. h4>Significance of this study/h4> h4>What is already known on this subject?/h4> The protective effect of preemptive appendectomy is currently investigated as a therapy for refractory ulcerative colitis (UC), with encouraging results. An increased risk of developing colitis-associated cancer (CAC) caused by this promising treatment has been identified. Since it is commonly accepted that CAC is related to colitis severity and extent, this finding is counterintuitive and the mechanisms of this paradoxical effect remain unknown. h4>What are the new findings?/h4> In a mouse model of CAC, less extended colitis associated with an increased number of tumors was observed. Intra-tumor T-cell infiltration was significantly reduced after appendectomy. Blocking lymphocyte trafficking to the colon with current or experimental UC treatments mimicked the appendectomy-associated phenotype whereas neo-appendicitis or appendix-primed T-cell injection in recipient mice increased intra-tumor T-cell infiltration and strengthened protection against CAC. In UC patients with CAC, appendectomy was associated with a decreased intra-tumor T-cell infiltration. These findings suggest that, in UC, appendectomy could suppress a major site of T-cell priming in the colon, resulting in a reduced CAC immunosurveillance. h4>How might it impact on clinical practice in the foreseeable future?/h4> This work emphasizes the fact that precautions will be necessary if appendectomy becomes an accepted therapeutic option for the treatment of refractory UC. Innovative cell-based therapies and immunotherapies, such as the administration of stimulated autologous appendicular T cells in patients with CAC are promising options.
- Immunology and Microbiology
CD4+ CD8αα+ T Cells in the Gastric epithelium Mediate Chronic Inflammation Induced by Helicobacter Felis
Preprint on Research Square on 9 February 2021 by Ruan, G., Huang, A., et al.
PubMed
CD4+ CD8αα+ double-positive intraepithelial T lymphocytes (DP T cells), a newly characterized subset of intraepithelial T cell, has been reported to contribute to local immunosuppression. However, whether DP T cells are present in Helicobacter. pylori- induced gastritis, and their relationship with disease prognosis remain to be elucidated. In this study, We established chronic gastritis models through Helicobacter felis ( H. felis ) infection. Gastric infiltrating lymphocytes were isolated from H. felis -induced gastritis mice and analyzed by flow cytometry. Our results suggest that DP T cells frequency in H. felis -induced gastritis mice was higher than the uninfected mice. Gastric DP T cells derived from lamina propria cells, which distributed in the gastric epithelial layer. We found that DP T cells exhibited anti-inflammatory function. In vitro , DP T cells inhibited the maturation of dendritic cells and the proliferation of CD4+ T cell. The elimination of CD4+CD8αα+ T cells in vivo resulted in severe gastritis and a reduction of H. felis load. Additionally, vaccine with silk fibroin as delivery systems enhanced vaccine efficacy by reducing DP T cells. We demonstrated that DP T cells performed an immunosuppressive role in Helicobacter felis -induced gastritis. These findings revealed that DP T cells may affect the prognosis of the disease and the vaccine efficacy.
- In Vivo,
- Mus musculus (House mouse),
- Immunology and Microbiology
Inhibiting PGGT1B Disrupts Function of RHOA, Resulting in T-cell Expression of Integrin α4β7 and Development of Colitis in Mice.
In Gastroenterology on 1 November 2019 by López-Posadas, R., Fastancz, P., et al.
PubMed
It is not clear how regulation of T-cell function is altered during development of inflammatory bowel diseases (IBD). We studied the mechanisms by which geranylgeranyltransferase-mediated prenylation controls T-cell localization to the intestine and chronic inflammation.We generated mice with T-cell-specific disruption of the geranylgeranyltransferase type I, beta subunit gene (Pggt1b), called Pggt1bΔCD4 mice, or the ras homolog family member A gene (Rhoa), called RhoaΔCD4 mice. We also studied mice with knockout of CDC42 or RAC1 and wild-type mice (controls). Intestinal tissues were analyzed by histology, multiphoton and confocal microscopy, and real-time polymerase chain reaction. Activation of CDC42, RAC1, and RHOA were measured with G-LISA, cell fractionation, and immunoblots. T cells and lamina propria mononuclear cells from mice were analyzed by flow cytometry or transferred to Rag1-/- mice. Mice were given injections of antibodies against integrin alpha4beta7 or gavaged with the RORC antagonist GSK805. We obtained peripheral blood and intestinal tissue samples from patients with and without IBD and analyzed them by flow cytometry.Pggt1bΔCD4 mice developed spontaneous colitis, characterized by thickening of the intestinal wall, edema, fibrosis, accumulation of T cells in the colon, and increased expression of inflammatory cytokines. Compared with control CD4+ T cells, PGGT1B-deficient CD4+ T cells expressed significantly higher levels of integrin alpha4beta7, which regulates their localization to the intestine. Inflammation induced by transfer of PGGT1B-deficient CD4+ T cells to Rag1-/- mice was blocked by injection of an antibody against integrin alpha4beta7. Lamina propria of Pggt1bΔCD4 mice had increased numbers of CD4+ T cells that expressed RORC and higher levels of cytokines produced by T-helper 17 cells (granulocyte-macrophage colony-stimulating factor, interleukin [IL]17A, IL17F, IL22, and tumor necrosis factor [TNF]). The RORC inverse agonist GSK805, but not antibodies against IL17A or IL17F, prevented colitis in Pggt1bΔCD4 mice. PGGT1B-deficient CD4+ T cells had decreased activation of RHOA. RhoAΔCD4 mice had a similar phenotype to Pggt1bΔCD4 mice, including development of colitis, increased numbers of CD4+ T cells in colon, increased expression of integrin alpha4beta7 by CD4+ T cells, and increased levels of IL17A and other inflammatory cytokines in lamina propria. T cells isolated from intestinal tissues from patients with IBD had significantly lower levels of PGGT1B than tissues from individuals without IBD.Loss of PGGT1B from T cells in mice impairs RHOA function, increasing CD4+ T-cell expression of integrin alpha4beta7 and localization to colon, resulting in increased expression of inflammatory cytokines and colitis. T cells isolated from gut tissues from patients with IBD have lower levels of PGGT1B than tissues from patients without IBD.Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
- In Vivo,
- Mus musculus (House mouse),
- Immunology and Microbiology,
- Neuroscience
Disrupting Myelin-Specific Th17 Cell Gut Homing Confers Protection in an Adoptive Transfer Experimental Autoimmune Encephalomyelitis.
In Cell Reports on 8 October 2019 by Duc, D., Vigne, S., et al.
PubMed
Multiple sclerosis (MS) is a common autoimmune disease of the CNS. Although an association between MS and inflammatory bowel diseases is observed, the link connecting intestinal immune responses and neuroinflammation remains unclear. Here we show that encephalitogenic Th17 cells infiltrate the colonic lamina propria before neurological symptom development in two murine MS models, active and adoptive transfer experimental autoimmune encephalomyelitis (EAE). Specifically targeting Th17 cell intestinal homing by blocking the α4β7-integrin and its ligand MAdCAM-1 pathway impairs T cell migration to the large intestine and dampens EAE severity in the Th17 cell adoptive transfer model. Mechanistically, myelin-specific Th17 cells proliferate in the colon and affect gut microbiota composition. The beneficial effect of blocking the α4β7-integrin and its ligand MAdCAM-1 pathway on EAE is interdependent with gut microbiota. Those results show that disrupting myelin-specific Th17 cell trafficking to the large intestine harnesses neuroinflammation and suggests that the gut environment and microbiota catalyze the encephalitogenic properties of Th17 cells.Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
- In Vivo,
- Block,
- Mus musculus (House mouse),
- Immunology and Microbiology,
- Neuroscience
Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization.
In Nature Communications on 6 September 2016 by Bemark, M., Hazanov, H., et al.
PubMed
Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8(high)/GFP(+) NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured. They are α4β7-integrin(+)CD73(+)PD-L2(+)CD80(+) and at systemic sites mostly IgM(+), while 80% are IgA(+) in Peyer's patches. On reactivation, most memory B cells in Peyer's patches are GL7(-), but expand in germinal centres and acquire higher affinity and more mutations, demonstrating strong clonal selection. CCR9 expression is found only in Peyer's patches and appears critical for gut homing. Thus, gut mucosal memory possesses unique features not seen after systemic immunization.
- In Vivo,
- Mus musculus (House mouse),
- Immunology and Microbiology
Diverting T helper cell trafficking through increased plasticity attenuates autoimmune encephalomyelitis.
In The Journal of Clinical Investigation on 1 January 2014 by Califano, D., Sweeney, K. J., et al.
PubMed
Naive T helper cells differentiate into functionally distinct effector subsets that drive specialized immune responses. Recent studies indicate that some of the effector subsets have plasticity. Here, we used an EAE model and found that Th17 cells deficient in the transcription factor BCL11B upregulated the Th2-associated proteins GATA3 and IL-4 without decreasing RAR-related orphan receptor γ (RORγt), IL-17, and GM-CSF levels. Surprisingly, abnormal IL-4 production affected Th17 cell trafficking, diverting migration from the draining lymph nodes/CNS route to the mesenteric lymph nodes/gut route, which ameliorated EAE without overt colitis. T helper cell rerouting in EAE was dependent on IL-4, which enhanced retinoic acid (RA) production by dendritic cells, which further induced expression of gut-homing receptors CCR9 and α4β7 on Bcl11b-deficient CD4+ T cells. Furthermore, IL-4 treatment or Th2 immunization of wild-type mice with EAE caused no alteration in Th17 cytokines or RORγt, but diverted T helper cell trafficking to the gut, which improved EAE outcome without overt colitis. Our data demonstrate that Th17 cells are permissive to Th2 gene expression without affecting Th17 gene expression. This Th17 plasticity has an impact on trafficking, which is a critical component of the immune response and may represent a possible avenue for treating multiple sclerosis.