PMID- 22350221 OWN - NLM STAT- MEDLINE DCOM- 20120911 LR - 20220325 IS - 1573-2592 (Electronic) IS - 0271-9142 (Print) IS - 0271-9142 (Linking) VI - 32 IP - 3 DP - 2012 Jun TI - Modulation of mTOR effector phosphoproteins in blood basophils from allergic patients. PG - 565-73 LID - 10.1007/s10875-012-9651-x [doi] AB - The mammalian target of rapamycin (mTOR) pathway contributes to various immunoinflammatory processes. Yet, its potential involvement in basophil responses in allergy remains unclear. In this pilot study, we quantified two key mTOR effector phosphoproteins, the eukaryotic initiation factor 4E (peIF4E) and S6 ribosomal protein (pS6rp), in blood basophils from nut allergy patients (NA, N = 16) and healthy controls (HC, N = 13). Without stimulation in vitro, basophil peIF4E levels were higher in NA than HC subjects (P = 0.014). Stimulation with nut (offending) but not chicken / rice (non-offending) extract increased basophil peIF4E and pS6rp levels (+32%, P = 0.018, and +98%, P = 0.0026, respectively) in NA but not HC subjects, concomitant with increased surface levels of CD203c and CD63, both known to reflect basophil activation. Pre-treatment with the mTOR inhibitor rapamycin decreased pS6rp and CD203c responses in nut extract-stimulated basophils in NA subjects. Thus, basophil responses to offending allergens are associated with modulation of mTOR effector phosphoproteins. FAU - Gernez, Yael AU - Gernez Y AD - Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. FAU - Tirouvanziam, Rabindra AU - Tirouvanziam R FAU - Reshamwala, Neha AU - Reshamwala N FAU - Yu, Grace AU - Yu G FAU - Weldon, Brittany C AU - Weldon BC FAU - Galli, Stephen J AU - Galli SJ FAU - Herzenberg, Leonore A AU - Herzenberg LA FAU - Nadeau, Kari C AU - Nadeau KC LA - eng GR - U01 AI147462/AI/NIAID NIH HHS/United States GR - R01 AI023990/AI/NIAID NIH HHS/United States GR - AI23990/AI/NIAID NIH HHS/United States GR - P20 ES018173/ES/NIEHS NIH HHS/United States GR - AI070813/AI/NIAID NIH HHS/United States GR - R01 CA072074/CA/NCI NIH HHS/United States GR - CA72074/CA/NCI NIH HHS/United States GR - R37 AI023990/AI/NIAID NIH HHS/United States GR - R01 AI070813/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120221 PL - Netherlands TA - J Clin Immunol JT - Journal of clinical immunology JID - 8102137 RN - 0 (Allergens) RN - 0 (Eukaryotic Initiation Factor-4E) RN - 0 (Plant Extracts) RN - 0 (Ribosomal Protein S6) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adolescent MH - Allergens/immunology/pharmacology MH - Anacardium/immunology MH - Basophils/drug effects/*immunology MH - Child MH - Child, Preschool MH - Eukaryotic Initiation Factor-4E/*immunology MH - Female MH - Humans MH - Juglans/immunology MH - Male MH - Nut Hypersensitivity/blood/*immunology MH - Peanut Hypersensitivity/blood/*immunology MH - Phosphorylation MH - Plant Extracts/immunology/pharmacology MH - Ribosomal Protein S6/*immunology MH - Sirolimus/pharmacology MH - TOR Serine-Threonine Kinases/antagonists & inhibitors/*immunology MH - Young Adult PMC - PMC4161465 MID - NIHMS606227 COIS- Competing interest statement The authors declare to hold no conflict of interest with the publication of the results included in this manuscript. EDAT- 2012/02/22 06:00 MHDA- 2012/09/12 06:00 PMCR- 2014/09/11 CRDT- 2012/02/22 06:00 PHST- 2011/08/01 00:00 [received] PHST- 2012/01/10 00:00 [accepted] PHST- 2012/02/22 06:00 [entrez] PHST- 2012/02/22 06:00 [pubmed] PHST- 2012/09/12 06:00 [medline] PHST- 2014/09/11 00:00 [pmc-release] AID - 10.1007/s10875-012-9651-x [doi] PST - ppublish SO - J Clin Immunol. 2012 Jun;32(3):565-73. doi: 10.1007/s10875-012-9651-x. Epub 2012 Feb 21.