Gut microbiota-CRAMP axis shapes intestinal barrier function and immune responses in dietary gluten-induced enteropathy.
In the gut, cathelicidin-related antimicrobial peptide (CRAMP) has been largely described for its anti-infective activities. With an increasing recognition of its immune regulatory effects in extra-intestinal diseases, the role of CRAMP in gluten-induced small intestinal enteropathy celiac disease remains unknown. This study aimed to investigate the unexplored role of CRAMP in celiac disease. By applying a mouse model of gluten-induced enteropathy (GIE) recapitulating small intestinal enteropathy of celiac disease, we observed defective CRAMP production in duodenal epithelium during GIE. CRAMP-deficient mice were susceptible to the development of GIE. Exogenous CRAMP corrected gliadin-triggered epithelial dysfunction and promoted regulatory immune responses at the intestinal mucosa. Additionally, GIE-associated gut dysbiosis with enriched Pseudomonas aeruginosa and production of the protease LasB contributed to defective intestinal CRAMP production. These results highlight microbiota-CRAMP axis in the modulation of barrier function and immune responses in GIE. Hence, modulating CRAMP may represent a therapeutic strategy for celiac disease.
Pubmed ID: 34125490 RIS Download
Research resources used in this publication
- Illumina (RRID:SCR_010233) (commercial organization)
- Black Zen software (RRID:SCR_018163) (software resource)
- ProteinSimple: FluorChem™ E System (RRID:SCR_013724) (tool)
- R Project for Statistical Computing (RRID:SCR_001905) (software resource)
- ImageJ (RRID:SCR_003070) (software resource)
- GraphPad Prism (RRID:SCR_002798) (software resource)
- FlowJo (RRID:SCR_008520) (software resource)
- Caco-2 (RRID:CVCL_0025) (cell line)
- B6.129X1-Camptm1Rlg/J (RRID:IMSR_JAX:017799) (organism)
- GemPharmatech (RRID:SCR_017239) (organism supplier)
Additional research tools detected in this publication
Antibodies used in this publication
- Anti-FITC MicroBeads (RRID:AB_244371)
- CD45RB Antibody, FITC (RRID:AB_2658357)
- Anti-Mouse CD25 Antibody, Biotin Conjugated (RRID:AB_871645)
- TCRγ/δ Antibody, anti-human, Biotin (RRID:AB_2733574)
- Ter-119 Antibody, anti-mouse, Biotin (RRID:AB_2784480)
- MHC Class II Antibody, anti-mouse, Biotin (RRID:AB_2660066)
- CD105 Antibody, anti-mouse, Biotin (RRID:AB_2660100)
- CD49b Antibody, anti-mouse, Biotin (RRID:AB_2660466)
- CD45R (B220) Antibody, anti-mouse, Biotin (RRID:AB_2819526)
- CD19 Antibody, anti-human, Biotin (RRID:AB_2726270)
- CD11c Antibody, anti-human, Biotin (RRID:AB_2726178)
- CD11b Antibody, anti-human/mouse, Biotin (RRID:AB_2726044)
- CD8a Antibody, anti-mouse, Biotin (RRID:AB_2733536)
- Rat Anti-Ly6g Monoclonal Antibody, Unconjugated, Clone RB6-8C5 (RRID:AB_470492)
- F4/80 antibody [CI:A3-1] (RRID:AB_1140040)
- Purified Mouse Anti-E-cadherin (RRID:AB_397580)
- CAMP antibody (RRID:AB_908736)
- Rat Anti-CD4 Monoclonal Antibody, PE-Cy7 Conjugated, Clone RM4-5 (RRID:AB_394461)
- ROR gamma (t) Monoclonal Antibody (B2D), PE, eBioscience (RRID:AB_10805392)
- Alexa Fluor(R) 488 anti-mouse FOXP3 (RRID:AB_1089114)
- APC anti-T-bet (RRID:AB_10896913)
- PE anti-mouse CD314 (NKG2D) (RRID:AB_1227713)
- Brilliant Violet 421(TM) anti-mouse CD3epsilon (RRID:AB_2562556)
- Brilliant Violet 421(TM) anti-mouse CX3CR1 (RRID:AB_2565706)
- APC anti-mouse CD103 (RRID:AB_1227503)
- Brilliant Violet 711(TM) anti-mouse CD11c (RRID:AB_2563905)
- Alexa Fluor(R) 700 anti-mouse CD45 (RRID:AB_493715)
- ACTB Monoclonal Antibody (RRID:AB_2768234)
- Anti-ZO-2 Polyclonal Antibody, Unconjugated (RRID:AB_88012)
- ZO-1 Polyclonal Antibody (RRID:AB_2533456)
- Phospho-NF-κB p65 (Ser536) (93H1) Rabbit mAb (RRID:AB_331284)
- MyD88 (D80F5) Rabbit mAb (RRID:AB_10547882)
- Akt (pan) (11E7) Rabbit mAb (RRID:AB_2225340)
- Phospho-Akt (Ser473) (D9E) XP® Rabbit mAb (RRID:AB_2315049)
- NFkB p65 antibody [E379] (RRID:AB_776751)
- TRAF6 antibody [EP592Y] (RRID:AB_778573)
- Haptoglobin antibody [EPSISR7] (RRID:AB_11157376)
- Anti-Occludin antibody (RRID:AB_2737295)
Associated grants
NonePublication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This is a list of tools and resources that we have found mentioned in this publication.
Miltenyi Biotec (tool)
RRID:SCR_008984
An Organization portal, Antibody supplier, Service resource,
View all literature mentionsC57BL/6J (tool)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsAnti-FITC MicroBeads (antibody)
RRID:AB_244371
This unknown targets FITC
View all literature mentionsCD45RB Antibody, FITC (antibody)
RRID:AB_2658357
This monoclonal targets CD45RB
View all literature mentionsAnti-Mouse CD25 Antibody, Biotin Conjugated (antibody)
RRID:AB_871645
This unknown targets Mouse CD25
View all literature mentionsTCRγ/δ Antibody, anti-human, Biotin (antibody)
RRID:AB_2733574
This monoclonal targets TCRγ/δ
View all literature mentionsTer-119 Antibody, anti-mouse, Biotin (antibody)
RRID:AB_2784480
This monoclonal targets Ter-119
View all literature mentionsMHC Class II Antibody, anti-mouse, Biotin (antibody)
RRID:AB_2660066
This monoclonal targets MHC Class II
View all literature mentionsCD105 Antibody, anti-mouse, Biotin (antibody)
RRID:AB_2660100
This monoclonal targets CD105
View all literature mentionsCD49b Antibody, anti-mouse, Biotin (antibody)
RRID:AB_2660466
This monoclonal targets CD49b
View all literature mentionsCD45R (B220) Antibody, anti-mouse, Biotin (antibody)
RRID:AB_2819526
This monoclonal targets CD45R (B220)
View all literature mentionsCD19 Antibody, anti-human, Biotin (antibody)
RRID:AB_2726270
This monoclonal targets CD19
View all literature mentionsCD11c Antibody, anti-human, Biotin (antibody)
RRID:AB_2726178
This monoclonal targets CD11c
View all literature mentionsCD11b Antibody, anti-human/mouse, Biotin (antibody)
RRID:AB_2726044
This monoclonal targets CD11b
View all literature mentionsCD8a Antibody, anti-mouse, Biotin (antibody)
RRID:AB_2733536
This monoclonal targets CD8a
View all literature mentionsRat Anti-Ly6g Monoclonal Antibody, Unconjugated, Clone RB6-8C5 (antibody)
RRID:AB_470492
This monoclonal targets Ly6g
View all literature mentionsF4/80 antibody [CI:A3-1] (antibody)
RRID:AB_1140040
This monoclonal targets F4/80 antibody [CI:A3-1]
View all literature mentionsPurified Mouse Anti-E-cadherin (antibody)
RRID:AB_397580
This monoclonal targets E-cadherin
View all literature mentionsRat Anti-CD4 Monoclonal Antibody, PE-Cy7 Conjugated, Clone RM4-5 (antibody)
RRID:AB_394461
This monoclonal targets CD4
View all literature mentionsROR gamma (t) Monoclonal Antibody (B2D), PE, eBioscience (antibody)
RRID:AB_10805392
This monoclonal targets ROR gamma (t)
View all literature mentionsAlexa Fluor(R) 488 anti-mouse FOXP3 (antibody)
RRID:AB_1089114
This monoclonal targets FOXP3
View all literature mentionsAPC anti-T-bet (antibody)
RRID:AB_10896913
This monoclonal targets T-bet
View all literature mentionsPE anti-mouse CD314 (NKG2D) (antibody)
RRID:AB_1227713
This monoclonal targets CD314
View all literature mentionsBrilliant Violet 421(TM) anti-mouse CD3epsilon (antibody)
RRID:AB_2562556
This monoclonal targets CD3epsilon
View all literature mentionsBrilliant Violet 421(TM) anti-mouse CX3CR1 (antibody)
RRID:AB_2565706
This monoclonal targets CX3CR1
View all literature mentionsAPC anti-mouse CD103 (antibody)
RRID:AB_1227503
This monoclonal targets CD103
View all literature mentionsBrilliant Violet 711(TM) anti-mouse CD11c (antibody)
RRID:AB_2563905
This monoclonal targets CD11c
View all literature mentionsAlexa Fluor(R) 700 anti-mouse CD45 (antibody)
RRID:AB_493715
This monoclonal targets CD45
View all literature mentionsACTB Monoclonal Antibody (antibody)
RRID:AB_2768234
This monoclonal targets ACTB
View all literature mentionsAnti-ZO-2 Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_88012
This polyclonal targets ZO-2
View all literature mentionsZO-1 Polyclonal Antibody (antibody)
RRID:AB_2533456
This polyclonal targets ZO-1
View all literature mentionsPhospho-NF-κB p65 (Ser536) (93H1) Rabbit mAb (antibody)
RRID:AB_331284
This monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsMyD88 (D80F5) Rabbit mAb (antibody)
RRID:AB_10547882
This monoclonal targets MyD88 (D80F5) Rabbit mAb
View all literature mentionsAkt (pan) (11E7) Rabbit mAb (antibody)
RRID:AB_2225340
This monoclonal targets Akt2
View all literature mentionsPhospho-Akt (Ser473) (D9E) XP® Rabbit mAb (antibody)
RRID:AB_2315049
This monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsNFkB p65 antibody [E379] (antibody)
RRID:AB_776751
This monoclonal targets Human NFkB p65
View all literature mentionsTRAF6 antibody [EP592Y] (antibody)
RRID:AB_778573
This monoclonal targets TRAF6
View all literature mentionsHaptoglobin antibody [EPSISR7] (antibody)
RRID:AB_11157376
This monoclonal targets Haptoglobin antibody [EPSISR7]
View all literature mentionsAnti-Occludin antibody (antibody)
RRID:AB_2737295
This monoclonal targets Occludin
View all literature mentionsIllumina (commercial organization)
RRID:SCR_010233
American company incorporated that develops, manufactures and markets integrated systems for the analysis of genetic variation and biological function. Provides a line of products and services that serve the sequencing, genotyping and gene expression and proteomics markets. Its headquarters are located in San Diego, California.
View all literature mentionsBlack Zen software (software resource)
RRID:SCR_018163
Software used to analyze images obtained from microscope. ZEN Black is software Zeiss uses to run their laser-based instruments.
View all literature mentionsProteinSimple: FluorChem™ E System (tool)
RRID:SCR_013724
Imaging system for detection of chemiluminescent, colorimetric and UV fluorescent gels and blots.
View all literature mentionsR Project for Statistical Computing (software resource)
RRID:SCR_001905
Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsImageJ (software resource)
RRID:SCR_003070
Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsGraphPad Prism (software resource)
RRID:SCR_002798
Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsFlowJo (software resource)
RRID:SCR_008520
Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsCaco-2 (cell line)
RRID:CVCL_0025
Cell line Caco-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsB6.129X1-Camptm1Rlg/J (organism)
RRID:IMSR_JAX:017799
Mus musculus with name B6.129X1-Camptm1Rlg/J from IMSR.
View all literature mentionsGemPharmatech (organism supplier)
RRID:SCR_017239
Contract research organization that provides genetically engineered mouse models (GEMMs) and services to global preclinical Research and Development communities. Specializes in developing animal models using cutting edge gene-editing technologies with large collection of cKO/KO (conditional knockout/knockout) mice, humanized mice, immunodeficient mice, and germ-free mice.Provides preclinical services, including mouse model customization, pharmacology services such as drug efficacy testing and mouse phenotyping, CRISPR/Cas9 gene-editing, cryopreservation, rapid expansion, and customized breeding.
View all literature mentions
