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Stronger Toll-like receptor 1/2, 4, and 7/8 but less 9 responses in peripheral blood mononuclear cells in non-infectious exacerbated asthmatic children.
Immunobiology 2013; 218(2):192-200I

Abstract

Toll-like receptors (TLR) initiate innate and often affect adaptive immune response. This study aimed to determine if TLR response and T regulatory cell (Treg) function in peripheral blood mononuclear cells (PBMC) correlate with clinical severity in non-infectious asthma. TLR1-9 expression and representative response cytokine TNF-α, IL-6, and IFN-β secretions were analyzed after stimulation by TLR1-9 ligands from 17 non-infectious asthmatic children. TNF-α production was higher in TLR1/2 (median 385.4 vs. 250.3 pg/ml in 1 μg/ml Pam3CSK4, p=0.0078), TLR4 (2392.4 vs. 1355.9 in 1 μg/ml LPS; p=0.0005), and TLR7/8 (10,776.2 vs. 4237.0 pg/ml in 1 μg/ml R848, p=0.0079) of patients in exacerbation than those in convalescence and healthy controls despite equal TLR expression. TNF-α production stimulated by TLR9 agonist was significantly lower in exacerbation (17.7 vs. 34.9 pg/ml in 1 μg/ml ODN2216, p=0.0175), while IL-6 production had similar patterns but was significantly lower in TLR3 signaling (119.7 vs. 245.0 pg/ml in 0.1 μg/ml poly(I:C), p=0.0033). IFN-β production by TLR3 agonist also decreased in exacerbation but not statistically significant. Six older children showed decreased FOXP3 percentage in CD4+CD25(high) and decreased suppression capability in exacerbation but restored in stabilization (82.8% vs. 90.0%, p=0.0061 and 60.9% vs. 81.7%, p=0.0071; respectively). In conclusion, normalizing imbalanced TLR signaling and enhancing Treg cell capability may guide possible therapeutic strategies for non-infectious asthma in exacerbation.

Authors+Show Affiliations

Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22727330

Citation

Lee, Wen-I, et al. "Stronger Toll-like Receptor 1/2, 4, and 7/8 but Less 9 Responses in Peripheral Blood Mononuclear Cells in Non-infectious Exacerbated Asthmatic Children." Immunobiology, vol. 218, no. 2, 2013, pp. 192-200.
Lee WI, Yao TC, Yeh KW, et al. Stronger Toll-like receptor 1/2, 4, and 7/8 but less 9 responses in peripheral blood mononuclear cells in non-infectious exacerbated asthmatic children. Immunobiology. 2013;218(2):192-200.
Lee, W. I., Yao, T. C., Yeh, K. W., Chen, L. C., Ou, L. S., & Huang, J. L. (2013). Stronger Toll-like receptor 1/2, 4, and 7/8 but less 9 responses in peripheral blood mononuclear cells in non-infectious exacerbated asthmatic children. Immunobiology, 218(2), pp. 192-200. doi:10.1016/j.imbio.2012.04.002.
Lee WI, et al. Stronger Toll-like Receptor 1/2, 4, and 7/8 but Less 9 Responses in Peripheral Blood Mononuclear Cells in Non-infectious Exacerbated Asthmatic Children. Immunobiology. 2013;218(2):192-200. PubMed PMID: 22727330.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stronger Toll-like receptor 1/2, 4, and 7/8 but less 9 responses in peripheral blood mononuclear cells in non-infectious exacerbated asthmatic children. AU - Lee,Wen-I, AU - Yao,Tsung-Chieh, AU - Yeh,Kuo-Wei, AU - Chen,Li-Chen, AU - Ou,Liang-Shiou, AU - Huang,Jing-Long, AU - ,, Y1 - 2012/05/22/ PY - 2011/08/02/received PY - 2012/03/08/revised PY - 2012/04/19/accepted PY - 2012/6/26/entrez PY - 2012/6/26/pubmed PY - 2013/7/5/medline SP - 192 EP - 200 JF - Immunobiology JO - Immunobiology VL - 218 IS - 2 N2 - Toll-like receptors (TLR) initiate innate and often affect adaptive immune response. This study aimed to determine if TLR response and T regulatory cell (Treg) function in peripheral blood mononuclear cells (PBMC) correlate with clinical severity in non-infectious asthma. TLR1-9 expression and representative response cytokine TNF-α, IL-6, and IFN-β secretions were analyzed after stimulation by TLR1-9 ligands from 17 non-infectious asthmatic children. TNF-α production was higher in TLR1/2 (median 385.4 vs. 250.3 pg/ml in 1 μg/ml Pam3CSK4, p=0.0078), TLR4 (2392.4 vs. 1355.9 in 1 μg/ml LPS; p=0.0005), and TLR7/8 (10,776.2 vs. 4237.0 pg/ml in 1 μg/ml R848, p=0.0079) of patients in exacerbation than those in convalescence and healthy controls despite equal TLR expression. TNF-α production stimulated by TLR9 agonist was significantly lower in exacerbation (17.7 vs. 34.9 pg/ml in 1 μg/ml ODN2216, p=0.0175), while IL-6 production had similar patterns but was significantly lower in TLR3 signaling (119.7 vs. 245.0 pg/ml in 0.1 μg/ml poly(I:C), p=0.0033). IFN-β production by TLR3 agonist also decreased in exacerbation but not statistically significant. Six older children showed decreased FOXP3 percentage in CD4+CD25(high) and decreased suppression capability in exacerbation but restored in stabilization (82.8% vs. 90.0%, p=0.0061 and 60.9% vs. 81.7%, p=0.0071; respectively). In conclusion, normalizing imbalanced TLR signaling and enhancing Treg cell capability may guide possible therapeutic strategies for non-infectious asthma in exacerbation. SN - 1878-3279 UR - https://www.unboundmedicine.com/medline/citation/22727330/Stronger_Toll_like_receptor_1/2_4_and_7/8_but_less_9_responses_in_peripheral_blood_mononuclear_cells_in_non_infectious_exacerbated_asthmatic_children_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0171-2985(12)00085-X DB - PRIME DP - Unbound Medicine ER -