Role of PTX3 in allergic airway inflammation
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Date
2013-05, 2013-05, 2016-07
Authors
Balhara, Jyoti
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Immunology
Frontiers in Immunology
Journal of Allergy and Clinical Immunology
Frontiers in Immunology
Journal of Allergy and Clinical Immunology
Abstract
Thesis Abstract:
Pentraxin 3 (PTX3) is a pattern recognition receptor that plays an important role in providing immunity against various pulmonary inflammatory conditions. Having known its role in fostering lung immunity, aim of my PhD thesis was to examine the role of PTX3 in asthma. In my thesis, I showed an enhanced level of PTX3 in the airway fluid of severe asthmatics and also in the airway fluid and the lungs of allergen exposed mice. To further investigate the role of PTX3, I used a murine model of ovalbumin (OVA)-induced experimental asthma and performed experiments on PTX3+/+ and PTX3-/- mice. I observed an enhanced airway inflammation and hyperactivity in OVA-exposed PTX3 Knockout (PTX3-/-) mice.
In PTX3-/- mice, there was an IL-17A dominant inflammation as compared to PTX3+/+ mice upon OVA challenge. This response was accompanied with increased CD4 T cell survival and reduced IL-2 production by these cells. As Th17 phenotype of CD4 T cells is shaped by IL-6 and IL-23 producing dendritic cells, we observed increased preponderance of such DCs in the lungs and the draining lymph nodes of PTX3-/- mice as compared to their PTX3+/+ counterparts, plausibly supporting Th17/ IL-17A dominant inflammation in the former.
Furthermore, there was increased infiltration of inflammatory DCs in the lungs in PTX3-/- mice upon OVA exposure. This observation was in line with increased generation of common myeloid progenitors in the bone marrow of these mice. PTX3-/- DCs showed reduced MHCII expression but increased surface expression of CD80 and CD86 along with increased ability of PTX3-/- DCs to uptake and process OVA. Since these DCs showed increase IL-6 and IL-23 production, co-culture of PTX3-/- DCs with OT II CD4 T cells resulted in greater IL-17A production as compared to those that were co-cultured with PTX3+/+ DCs.
Altogether, I have observed that deletion of PTX3 resulted in enhanced IL-17 immune response plausibly through increased IL-6 and IL-23 producing DCs in OVA-exposed mice. In summary, findings of my thesis provide insights of the novel regulatory role of PTX3 in allergic inflammation, primarily in context with CD4 T cell-DC axis.
Description
Keywords
asthma, inflammation
Citation
Balhara, J., L. Shan, and A. Soussi Gounni. PTX3 modulates airway hyperresponsiveness and immune response to OVA in a murine model of asthma (P6011). The Journal of Immunology 190:120.126.
Balhara, J., Koussih, L., Zhang, J., & Gounni, A. S. (2013). Pentraxin 3: An Immuno-Regulator in the Lungs. Frontiers in Immunology, 4, 127. http://doi.org/10.3389/fimmu.2013.00127
Balhara, J., L. Shan, J. Zhang, A. Muhuri, A. J. Halayko, M. S. Almiski, D. Doeing, J. McConville, M. M. Matzuk, and A. S. Gounni. Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival. Journal of Allergy and Clinical Immunology.
Balhara, J., Koussih, L., Zhang, J., & Gounni, A. S. (2013). Pentraxin 3: An Immuno-Regulator in the Lungs. Frontiers in Immunology, 4, 127. http://doi.org/10.3389/fimmu.2013.00127
Balhara, J., L. Shan, J. Zhang, A. Muhuri, A. J. Halayko, M. S. Almiski, D. Doeing, J. McConville, M. M. Matzuk, and A. S. Gounni. Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival. Journal of Allergy and Clinical Immunology.