CoChat
Sign Up
Cited by 10

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Schistosoma japonicum-derived peptide SJMHE1 ameliorates allergic symptoms and responses in mice with allergic rhinitis

Gao, Xuerong, Mao, Chaoming, Zheng, Tingting, Xu, Xiaowei, Luo, Xinkai, Zhang, Shan, Liu, Jiameng, Wang, Xuefeng, Chen, Xiaojun, Dong, Liyang·2023·Frontiers in Cellular and Infection Microbiology
DOI 10.3389/fcimb.2023.1143950PMC PMC10279851
Open this paper in CoChat — free account

Abstract

Helminth derived excretory/secretory molecules have shown efficacy in the treatment of allergic asthma in mice, but their roles in allergic rhinitis (AR) are little known. In this study, we aimed to determine the intervention effect of SJMHE1, a Schistosoma japonicum derived small molecular peptide, on ovalbumin (OVA)-induced AR mice and investigate its possible mechanism. AR was induced in BALB/c mice, following which the mice were treated with phosphate-buffered saline (PBS), OVA 323-339 and SJMHE1 respectively. SJMHE1 treatment improved clinical symptoms (rubbing and sneezing), suppressed infiltrates of inflammatory cells and eosinophils in nasal mucosa, modulated the production of type-2 (IL-4 and IL-13) and anti-inflammatory (IL-10) cytokines in the nasal lavage fluids (NLF), spleen, and serum. To investigate the underlying mechanism, fluorescein isothiocyanate (FITC)-labeled SJMHE1 was subcutaneously injected into AR mice, and we found that the FITC-SJMHE1 could accumulate in spleen, but not in nasal mucosa. FITC-SJMHE1 mainly bound to CD19 positive cells (B cells), and the SJMHE1 treatment significantly increased the proportion of regulatory B cells (Bregs) and B10 cells, along with the enhancement of PR domain containing protein 1 (Prdm1) protein levels. SJMHE1 may alleviate AR by upregulating Bregs, and has great potential as a new avenue for the AR treatment.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fcimb.2023.1143950

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Experimental protocol for the development of allergic rhinitis and treatment with SJMHE1. BALB/c mice were sensitized with OVA and aluminum hydroxide in PBS on days 0, 7 and 14 by intraperitoneal injection (i.p.). Subsequently, the sensitized mice were challenged intranasally with OVA daily from days 21 to 27 and 29 to 35. PBS, emulsified OVA323-339 or SJMHE1 with incomplete Freund’s adjuvant were subcutaneously (inner thigh) injected into mice on days 0, 14 and 28. The mice were sacrificed on day 36 and the samples were collected.
Figure 1 Experimental protocol for the development of allergic rhinitis and treatment with SJMHE1. BALB/c mice were sensitized with OVA and aluminum hydroxide in PBS on days 0, 7 and 14 by intraperitoneal injection (i.p.). Subsequently, the sensitized mice were challenged intranasally with OVA daily from days 21 to 27 and 29 to 35. PBS, emulsified OVA323-339 or SJMHE1 with incomplete Freund’s adjuvant were subcutaneously (inner thigh) injected into mice on days 0, 14 and 28. The mice were sacrificed on day 36 and the samples were collected.CC BY · PubMed Central
Figure 2 SJMHE1 treatment inhibits nasal rubbing and sneezes in allergic mice. The number of nasal rubbing (A) and sneezes movements (B) was counted for 20 min immediately after the last nasal challenge. Data are presented as mean ± SD (n = 11) from three independent experiments. Each dot represents data from one animal. (C) Representative image showing nasal external skin lesion induced by scratching. One-way analysis of variance (Tukey Kramer post hoc tests): **P<0.01, ***P<0.001.
Figure 2 SJMHE1 treatment inhibits nasal rubbing and sneezes in allergic mice. The number of nasal rubbing (A) and sneezes movements (B) was counted for 20 min immediately after the last nasal challenge. Data are presented as mean ± SD (n = 11) from three independent experiments. Each dot represents data from one animal. (C) Representative image showing nasal external skin lesion induced by scratching. One-way analysis of variance (Tukey Kramer post hoc tests): **P<0.01, ***P<0.001.CC BY · PubMed Central
Figure 3 SJMHE1 treatment inhibits the development of nasal mucosa inflammation in allergic mice. (A) Representative photographs of HE-stained nasal mucosa sections from each group. 20× magnification. (B) Histological analysis of nasal mucosa from mice by Wright-Giemsa staining. 100× magnification. Representative images are showed. (C) The number of eosinophils in nasal mucosa was measured microscopically. Data are presented as mean ± SD (n = 11) from three independent experiments. Each dot represents data from one animal. One-way analysis of variance (Tukey Kramer post hoc tests): ***P<0.001.
Figure 3 SJMHE1 treatment inhibits the development of nasal mucosa inflammation in allergic mice. (A) Representative photographs of HE-stained nasal mucosa sections from each group. 20× magnification. (B) Histological analysis of nasal mucosa from mice by Wright-Giemsa staining. 100× magnification. Representative images are showed. (C) The number of eosinophils in nasal mucosa was measured microscopically. Data are presented as mean ± SD (n = 11) from three independent experiments. Each dot represents data from one animal. One-way analysis of variance (Tukey Kramer post hoc tests): ***P<0.001.CC BY · PubMed Central
Figure 4 SJMHE1 treatment modulates the expression of cytokines in nasal lavage fluid (NLF) of allergic mice. On day 36, the mice were killed, and the NLF from each mouse was tested by ELISA. Statistical analysis of IL-4 (A), IL-13 (B) and IL-10 (C) levels in the NLF. Data are presented as mean ± SD (n = 9-11) from three independent experiments. Each dot represents data from one animal. One-way analysis of variance (Tukey Kramer post hoc tests): *P<0.05, **P<0.01, ***P<0.001.
Figure 4 SJMHE1 treatment modulates the expression of cytokines in nasal lavage fluid (NLF) of allergic mice. On day 36, the mice were killed, and the NLF from each mouse was tested by ELISA. Statistical analysis of IL-4 (A), IL-13 (B) and IL-10 (C) levels in the NLF. Data are presented as mean ± SD (n = 9-11) from three independent experiments. Each dot represents data from one animal. One-way analysis of variance (Tukey Kramer post hoc tests): *P<0.05, **P<0.01, ***P<0.001.CC BY · PubMed Central
Figure 5 SJMHE1 accumulates in spleen and regulates the systemic immune response in AR mice. (A) Immunofluorescence of FITC-SJMHE1 (green) in nasal mucosa and spleen of mice at day 3, 7, and 14 after FITC-SJMHE1 treatment. Quantitative analysis for relative IL-4 (B), IL-13 (C) and IL-10 (D) genes expression in the spleen of mice. Data are presented as mean ± SD (n = 11) from two independent experiments. Each dot represents data from one animal. (E–G) Statistical analysis of IL-4, IL-13 and IL-10 levels in the serum, respectively. Data are presented as mean ± SD (n = 11) from three independent experiments. Each dot represents data from one animal. (H) OVA-specific IgE level in serum of mice. Data are presented as mean ± SD (n = 11) from three independent experiments. Each dot represents data from one animal. One-way analysis of variance (Tukey Kramer post hoc tests): *P<0.05, **P<0.01, ***P<0.001.
Figure 5 SJMHE1 accumulates in spleen and regulates the systemic immune response in AR mice. (A) Immunofluorescence of FITC-SJMHE1 (green) in nasal mucosa and spleen of mice at day 3, 7, and 14 after FITC-SJMHE1 treatment. Quantitative analysis for relative IL-4 (B), IL-13 (C) and IL-10 (D) genes expression in the spleen of mice. Data are presented as mean ± SD (n = 11) from two independent experiments. Each dot represents data from one animal. (E–G) Statistical analysis of IL-4, IL-13 and IL-10 levels in the serum, respectively. Data are presented as mean ± SD (n = 11) from three independent experiments. Each dot represents data from one animal. (H) OVA-specific IgE level in serum of mice. Data are presented as mean ± SD (n = 11) from three independent experiments. Each dot represents data from one animal. One-way analysis of variance (Tukey Kramer post hoc tests): *P<0.05, **P<0.01, ***P<0.001.CC BY · PubMed Central
Figure 6 SJMHE1 binds to B cells in the spleen and upregulates the ratio of Bregs and B10 cells. (A) The percentages of CD4+FITC+ cells, CD19+FITC+ cells, CD11c+FITC+ cells and F4/80+FITC+ cells in spleen were analyzed by flow cytometry, and (B) percentage of CD19+ cells is shown (n = 3-5). (C) Splenocytes from mice were enriched for CD19+ cells using a flow cytometry sorter. (D) Gene expression profiles of the PBS and SJMHE1 groups were clustered in an unsupervised hierarchical manner. The heat map of differentially expressed genes identified by clustering analysis is shown in the figure. Each column represents a sample and each row represents a gene. Red and blue colors indicate genes with up- and down-regulated expression, respectively. (E) Dot plot shows 454 significantly differentially expressed (P < 0.05 and |log2FC| > 1) genes with 292 downregulated and 162 upregulated in the SJMHE1 group. FC: fold change. (F) Real-time PCR analysis of Hspa1a and Hspa1b mRNA levels in CD19+ B cells isolated from mouse splenocytes (n = 3). (G, H) Percentages of CD19+IL-10+ cells. Data are presented as mean ± SD (n = 9-11) from three independent experiments. Each dot represents data from one animal. (I, J) IL-10+ B-cell frequencies gated on CD1dhiCD5+ (n = 3-5). (K) Prmd1 expression in spleen of mice was detected by Western blotting (n = 2-3). One-way analysis of variance (Tukey Kramer post hoc tests) and Student’s t test: **P<0.01, ***P<0.001.
Figure 6 SJMHE1 binds to B cells in the spleen and upregulates the ratio of Bregs and B10 cells. (A) The percentages of CD4+FITC+ cells, CD19+FITC+ cells, CD11c+FITC+ cells and F4/80+FITC+ cells in spleen were analyzed by flow cytometry, and (B) percentage of CD19+ cells is shown (n = 3-5). (C) Splenocytes from mice were enriched for CD19+ cells using a flow cytometry sorter. (D) Gene expression profiles of the PBS and SJMHE1 groups were clustered in an unsupervised hierarchical manner. The heat map of differentially expressed genes identified by clustering analysis is shown in the figure. Each column represents a sample and each row represents a gene. Red and blue colors indicate genes with up- and down-regulated expression, respectively. (E) Dot plot shows 454 significantly differentially expressed (P < 0.05 and |log2FC| > 1) genes with 292 downregulated and 162 upregulated in the SJMHE1 group. FC: fold change. (F) Real-time PCR analysis of Hspa1a and Hspa1b mRNA levels in CD19+ B cells isolated from mouse splenocytes (n = 3). (G, H) Percentages of CD19+IL-10+ cells. Data are presented as mean ± SD (n = 9-11) from three independent experiments. Each dot represents data from one animal. (I, J) IL-10+ B-cell frequencies gated on CD1dhiCD5+ (n = 3-5). (K) Prmd1 expression in spleen of mice was detected by Western blotting (n = 2-3). One-way analysis of variance (Tukey Kramer post hoc tests) and Student’s t test: **P<0.01, ***P<0.001.CC BY · PubMed Central
Figure 7 Breg cells can be generated in vitro by direct interaction with SJMHE1. (A, B) Splenic B cells from naïve mice were cultured for 24 h with SJMHE1 (0.5 μg/ml), OVA323-339 (0.5 μg/ml), or medium. Intracellular IL-10 expression of total B cells after addition of PMA/ionomycin and monenisn to the last 4 hours of the culture was determined by flow cytometry. Data are presented as mean ± SD (n = 9) from three independent experiments. (C) Splenic B cells from naïve mice were cultured with SJMHE1 (0.5 μg/ml) for 24 hours, and the protein levels of IL-10 in the supernatant were detected by ELISA. Data are presented as mean ± SD (n = 6) from two independent experiments. One-way analysis of variance (Tukey Kramer post hoc tests): ***P<0.001.
Figure 7 Breg cells can be generated in vitro by direct interaction with SJMHE1. (A, B) Splenic B cells from naïve mice were cultured for 24 h with SJMHE1 (0.5 μg/ml), OVA323-339 (0.5 μg/ml), or medium. Intracellular IL-10 expression of total B cells after addition of PMA/ionomycin and monenisn to the last 4 hours of the culture was determined by flow cytometry. Data are presented as mean ± SD (n = 9) from three independent experiments. (C) Splenic B cells from naïve mice were cultured with SJMHE1 (0.5 μg/ml) for 24 hours, and the protein levels of IL-10 in the supernatant were detected by ELISA. Data are presented as mean ± SD (n = 6) from two independent experiments. One-way analysis of variance (Tukey Kramer post hoc tests): ***P<0.001.CC BY · PubMed Central
Figure 8 Biocompatibility evaluation of SJMHE1. (A) Schematic diagram for SJMHE1 treatment. (B) HE staining. (C) Body weight of mice. (D, E) The indicators reflecting the physiological functions of the liver (ALT and AST) and kidneys (CREA and UREA) were tested. Each dot represents data from one animal, and data are presented as mean ± SD (n = 10) from three independent experiments. Student’ s t test.
Figure 8 Biocompatibility evaluation of SJMHE1. (A) Schematic diagram for SJMHE1 treatment. (B) HE staining. (C) Body weight of mice. (D, E) The indicators reflecting the physiological functions of the liver (ALT and AST) and kidneys (CREA and UREA) were tested. Each dot represents data from one animal, and data are presented as mean ± SD (n = 10) from three independent experiments. Student’ s t test.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 40

  1. Amu, 2010, Regulatory b cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model, J. Allergy Clin. Immunol., 125, 1114, 10.1016/j.jaci.2010.01.018 · DOI
  2. Bohnacker, 2020, What can parasites tell us about the pathogenesis and treatment of asthma and allergic diseases, Front. Immunol., 11, 10.3389/fimmu.2020.02106 · DOI · Paper page
  3. Bousquet, 2020, Allergic rhinitis, Nat. Rev. Dis. Primers, 6, 95, 10.1038/s41572-020-00227-0 · DOI
  4. Braza, 2014, Regulatory functions of b cells in allergic diseases, Allergy, 69, 1454, 10.1111/all.12490 · DOI
  5. Brozek, 2017, Allergic rhinitis and its impact on asthma (ARIA) guidelines-2016 revision, J. Allergy Clin. Immunol., 140, 950, 10.1016/j.jaci.2017.03.050 · DOI
  6. Coltherd, 2016, The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma, Sci. Rep., 6, 10.1038/srep19224 · DOI
  7. Dong, 2014, Decreased expression of microRNA-21 correlates with the imbalance of Th17 and treg cells in patients with rheumatoid arthritis, J. Cell Mol. Med., 18, 2213, 10.1111/jcmm.12353 · DOI
  8. Dong, 2021, Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice, Stem Cell Res. Ther., 12, 4, 10.1186/s13287-020-02072-0 · DOI
  9. Eifan, 2016, Pathogenesis of rhinitis, Clin. Exp. Allergy, 46, 1139, 10.1111/cea.12780 · DOI · Paper page
  10. Fan, 2022, Roles of regulatory b cells in the pathogenesis of allergic rhinitis, Allergol Immunopathol. (Madr), 50, 7, 10.15586/aei.v50i5.615 · DOI
  11. Fang, 2021, Inhibition of TRPA1 reduces airway inflammation and hyperresponsiveness in mice with allergic rhinitis, FASEB J., 35, 10.1096/fj.201902627R · DOI
  12. Greiner, 2011, Allergic rhinitis, Lancet, 378, 2112, 10.1016/S0140-6736(11)60130-X · DOI
  13. Harnett, 2010, Helminth-derived immunomodulators: can understanding the worm produce the pill, Nat. Rev. Immunol., 10, 278, 10.1038/nri2730 · DOI
  14. Kim, 2016, Regulatory b cells and T follicular helper cells are reduced in allergic rhinitis, J. Allergy Clin. Immunol., 138, 1192, 10.1016/j.jaci.2016.03.017 · DOI
  15. Kosaka, 2011, IL-10 controls Th2-type cytokine production and eosinophil infiltration in a mouse model of allergic airway inflammation, Immunobiology, 216, 811, 10.1016/j.imbio.2010.12.003 · DOI
  16. Li, 2021, SJMHE1 peptide from schistosoma japonicum inhibits asthma in mice by regulating Th17/Treg cell balance via miR-155, J. Inflammation Res., 14, 5305, 10.2147/JIR.S334636 · DOI
  17. Li, 2022, Helminth-induced CD9(+) b-cell subset alleviates obesity-associated inflammation via IL-10 production, Int. J. Parasitol., 52, 111, 10.1016/j.ijpara.2021.08.009 · DOI
  18. Lothstein, 2021, Mining helminths for novel therapeutics, Trends Mol. Med., 27, 345, 10.1016/j.molmed.2020.12.010 · DOI
  19. Meng, 2019, Recent developments and highlights in allergic rhinitis, Allergy, 74, 2320, 10.1111/all.14067 · DOI
  20. Okada, 2010, The 'hygiene hypothesis' for autoimmune and allergic diseases: an update, Clin. Exp. Immunol., 160, 1, 10.1111/j.1365-2249.2010.04139.x · DOI
  21. Pipkorn, 1988, Methods for obtaining specimens from the nasal mucosa for morphological and biochemical analysis, Eur. Respir. J., 1, 856, 10.1183/09031936.93.01090856 · DOI
  22. Ren, 2016, Novel T-cell epitopes on schistosoma japonicum SjP40 protein and their preventive effect on allergic asthma in mice, Eur. J. Immunol., 46, 1203, 10.1002/eji.201545775 · DOI
  23. Rosser, 2015, Regulatory b cells: origin, phenotype, and function, Immunity, 42, 607, 10.1016/j.immuni.2015.04.005 · DOI · Paper page
  24. Rzepecka, 2014, Small molecule analogues of the immunomodulatory parasitic helminth product ES-62 have anti-allergy properties, Int. J. Parasitol., 44, 669, 10.1016/j.ijpara.2014.05.001 · DOI · Paper page
  25. Schroder, 2003, Heat shock protein 70 genotypes HSPA1B and HSPA1L influence cytokine concentrations and interfere with outcome after major injury, Crit. Care Med., 31, 73, 10.1097/00003246-200301000-00011 · DOI
  26. Shan, 2021, Schistosoma japonicum peptide SJMHE1 inhibits acute and chronic colitis induced by dextran sulfate sodium in mice, Parasit Vectors, 14, 455, 10.1186/s13071-021-04977-y · DOI
  27. Stanic, 2015, IL-10-overexpressing b cells regulate innate and adaptive immune responses, J. Allergy Clin. Immunol., 135, 771, 10.1016/j.jaci.2014.07.041 · DOI
  28. Suzuki, 2020, Intranasal administration of regulatory dendritic cells is useful for the induction of nasal mucosal tolerance in a mice model of allergic rhinitis, World Allergy Organ J., 13, 10.1016/j.waojou.2020.100447 · DOI
  29. van der Vlugt, 2012, Schistosomes induce regulatory features in human and mouse CD1d(hi) b cells: inhibition of allergic inflammation by IL-10 and regulatory T cells, PLoS One, 7, 10.1371/journal.pone.0030883 · DOI
  30. van der Vlugt, 2014, Interleukin 10 (IL-10)-producing CD1dhi regulatory b cells from schistosoma haematobium-infected individuals induce IL-10-positive T cells and suppress effector T-cell cytokines, J. Infect. Dis., 210, 1207, 10.1093/infdis/jiu257 · DOI
  31. Wang, 2021, HSP70, a novel regulatory molecule in b cell-mediated suppression of autoimmune diseases, J. Mol. Biol., 433, 166634, 10.1016/j.jmb.2020.08.019 · DOI
  32. Wang, 2019, Changes among TGF-beta1(+) breg cells and helper T cell subsets in a murine model of allergic rhinitis with prolonged OVA challenge, Int. Immunopharmacol, 69, 347, 10.1016/j.intimp.2019.01.009 · DOI
  33. Wang, 2017, Inhibition of cytokine response to TLR stimulation and alleviation of collagen-induced arthritis in mice by schistosoma japonicum peptide SJMHE1, J. Cell Mol. Med., 21, 475, 10.1111/jcmm.12991 · DOI
  34. Wang, 2020, The blockade of PD-1/PD-L1 pathway promotes the apoptosis of CD19(+) CD25(+) bregs and suppresses the secretion of IL-10 in patients with allergic rhinitis, Scand. J. Immunol., 91, 10.1111/sji.12836 · DOI
  35. Wang, 2019, Blimp-1 contributes to the development and function of regulatory b cells, Front. Immunol., 10, 10.3389/fimmu.2019.01909 · DOI
  36. Wang, 2016, Schistosoma japonicum HSP60-derived peptide SJMHE1 suppresses delayed-type hypersensitivity in a murine model, Parasit Vectors, 9, 147, 10.1186/s13071-016-1434-4 · DOI
  37. Wang, 2009, CD4+CD25+ treg induction by an HSP60-derived peptide SJMHE1 from schistosoma japonicum is TLR2 dependent, Eur. J. Immunol., 39, 3052, 10.1002/eji.200939335 · DOI
  38. Xie, 2021, Induction of the IL-10-producing regulatory b cell phenotype following trichinella spiralis infection, Mol. Immunol., 133, 86, 10.1016/j.molimm.2021.02.012 · DOI
  39. Yang, 2012, IL-10-producing regulatory B10 cells ameliorate collagen-induced arthritis via suppressing Th17 cell generation, Am. J. Pathol., 180, 2375, 10.1016/j.ajpath.2012.03.010 · DOI
  40. Zhang, 2019, Schistosoma japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice, J. Cell Mol. Med., 23, 7819, 10.1111/jcmm.14661 · DOI

Cited by

Sorted by citations

See all 10

Metadata

Authors
Gao, X., Mao, C., Zheng, T., Xu, X., Luo, X., Zhang, S., Liu, J., Wang, X., Chen, X., & Dong, L.
Venue
Frontiers in Cellular and Infection Microbiology
Publisher
Frontiers Media SA
Published
2023-06-06
Volume
13
ISSN
2235-2988
DOI
10.3389/fcimb.2023.1143950
PMC
PMC10279851
Cited by
10
References
3
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
National Natural Science Foundation of China

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review