The role of mTOR activation in steroid-resistant asthma: insights from particulate matter-induced mouse model and patient studies

Henderson I, Caiazzo E, McSharry C, Guzik TJ, Maffia P. Why do some asthma patients respond poorly to glucocorticoid therapy? Pharmacol Res. 2020;160:105189.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marshall CL, Hasani K, Mookherjee N. Immunobiology of steroid-unresponsive severe asthma. Front Allergy. 2021;2:718267.

Article  PubMed  PubMed Central  Google Scholar 

Rider CF, Carlsten C. Air pollution and resistance to inhaled glucocorticoids: evidence, mechanisms and gaps to fill. Pharmacol Ther. 2019;194:1–21.

Article  CAS  PubMed  Google Scholar 

Brandt EB, Bolcas PE, Ruff BP, Khurana Hershey GK. IL33 contributes to diesel pollution-mediated increase in experimental asthma severity. Allergy. 2020;75:2254–66.

Article  CAS  PubMed  Google Scholar 

Park CO, Kupper TS. The emerging role of resident memory T cells in protective immunity and inflammatory disease. Nat Med. 2015;21:688–97.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bosnjak B, Kazemi S, Altenburger LM, Mokrovic G, Epstein MM. Th2-T(RMs) maintain life-long allergic memory in experimental asthma in mice. Front Immunol. 2019;10:840.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wiest M, Upchurch K, Yin W, Ellis J, Xue Y, Lanier B, et al. Clinical implications of CD4(+) T cell subsets in adult atopic asthma patients. Allergy Asthma Clin Immunol. 2018;14:7.

Article  PubMed  PubMed Central  Google Scholar 

Palikhe NS, Laratta C, Nahirney D, Vethanayagam D, Bhutani M, Vliagoftis H, et al. Elevated levels of circulating CD4(+) CRTh2(+) T cells characterize severe asthma. Clin Exp Allergy. 2016;46:825–36.

Article  CAS  PubMed  Google Scholar 

Brandt EB, Biagini Myers JM, Acciani TH, Ryan PH, Sivaprasad U, Ruff B, et al. Exposure to allergen and diesel exhaust particles potentiates secondary allergen-specific memory responses, promoting asthma susceptibility. J Allergy Clin Immunol. 2015;136:295–303. e7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Perl A. mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging. Ann N Y Acad Sci. 2015;1346:33–44.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chi H. Regulation and function of mTOR signalling in T cell fate decisions. Nat Rev Immunol. 2012;12:325–38.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yin Y, Mitson-Salazar A, Wansley DL, Singh SP, Prussin C. Rapamycin preferentially inhibits human IL-5(+) T(H)2-cell proliferation via an mTORC1/S6 kinase-1-dependent pathway. J Allergy Clin Immunol. 2017;139:1701–e170410.

Article  CAS  PubMed  Google Scholar 

Kurebayashi Y, Nagai S, Ikejiri A, Ohtani M, Ichiyama K, Baba Y, et al. PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi1 expression and nuclear translocation of RORgamma. Cell Rep. 2012;1:360–73.

Article  CAS  PubMed  Google Scholar 

Park HW, Lee HS. IL-23 contributes to Particulate Matter induced allergic asthma in the early life of mice and promotes asthma susceptibility. J Mol Med (Berl). 2024;102:129–42.

Article  CAS  PubMed  Google Scholar 

Tramutola A, Lanzillotta C, Barone E, Arena A, Zuliani I, Mosca L, et al. Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome. Transl Neurodegener. 2018;7:28.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Krakauer T, Buckley M. Intranasal rapamycin rescues mice from staphylococcal enterotoxin B-induced shock. Toxins (Basel). 2012;4:718–28.

Article  CAS  PubMed  Google Scholar 

Yoshioka M, Sagara H, Takahashi F, Harada N, Nishio K, Mori A, et al. Role of multidrug resistance-associated protein 1 in the pathogenesis of allergic airway inflammation. Am J Physiol Lung Cell Mol Physiol. 2009;296:L30–6.

Article  CAS  PubMed  Google Scholar 

Park SC, Kim H, Bak Y, Shim D, Kwon KW, Kim CH, et al. An Alternative Dendritic Cell-Induced Murine Model of Asthma exhibiting a robust Th2/Th17-Skewed response. Allergy Asthma Immunol Res. 2020;12:537–55.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee HS, Park HW. Role of mTOR in the development of Asthma in mice with cigarette smoke-Induced Cellular Senescence. J Gerontol Biol Sci Med Sci. 2022;77:433–42.

Article  CAS  Google Scholar 

Sauter M, Sauter RJ, Nording H, Olbrich M, Emschermann F, Langer HF. Protocol to isolate and analyze mouse bone marrow derived dendritic cells (BMDC). STAR Protoc. 2022;3:101664.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lambrecht BN, Hammad H, Fahy JV. Cytokines. Asthma Immun. 2019;50:975–91.

CAS  Google Scholar 

Zhang X, Chang Li X, Xiao X, Sun R, Tian Z, Wei H. CD4(+)CD62L(+) central memory T cells can be converted to Foxp3(+) T cells. PLoS ONE. 2013;8:e77322.

Article  CAS  PubMed  PubMed Central  Google Scholar 

McMillan SJ, Sharma RS, McKenzie EJ, Richards HE, Zhang J, Prescott A, et al. Siglec-E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b beta2-integrin-dependent signaling. Blood. 2013;121:2084–94.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Loffredo LF, Coden ME, Jeong BM, Walker MT, Anekalla KR, Doan TC, et al. Eosinophil accumulation in postnatal lung is specific to the primary septation phase of development. Sci Rep. 2020;10:4425.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hirahara K, Kokubo K, Aoki A, Kiuchi M, Nakayama T. The role of CD4(+) Resident Memory T cells in local immunity in the mucosal tissue - protection Versus Pathology. Front Immunol. 2021;12:616309.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Caccamo N, Joosten SA, Ottenhoff THM, Dieli F. Atypical human effector/memory CD4(+) T cells with a naive-like phenotype. Front Immunol. 2018;9:2832.

Article  PubMed  PubMed Central  Google Scholar 

Fukunaga J, Abe M, Murai A, Akitake Y, Hosokawa M, Takahashi M. Comparative study to elucidate the mechanism underlying the difference in airway hyperresponsiveness between two mouse strains. Int Immunopharmacol. 2007;7:1852–61.

Article  CAS  PubMed  Google Scholar 

Blacquiere MJ, Hylkema MN, Postma DS, Geerlings M, Timens W, Melgert BN. Airway inflammation and remodeling in two mouse models of asthma: comparison of males and females. Int Arch Allergy Immunol. 2010;153:173–81.

Article  CAS  PubMed  Google Scholar 

Chen Z, Pan J, Jia Y, Li D, Min Z, Su X, et al. Effect of memory CD4(+) T cells’ signal transducer and activator of transcription (STATs) functional shift on cytokine-releasing properties in asthma. Cell Biol Toxicol. 2017;33:27–39.

Article  CAS  PubMed  Google Scholar 

Turner DL, Goldklang M, Cvetkovski F, Paik D, Trischler J, Barahona J, et al. Biased generation and in situ activation of lung tissue-resident memory CD4 T cells in the pathogenesis of allergic asthma. J Immunol. 2018;200:1561–9.

Comments (0)

No login
gif