{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:46:28Z","timestamp":1791117988592,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,1,19]],"date-time":"2007-01-19T00:00:00Z","timestamp":1169164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phosphoinositide 3\u2010kinases (PI3K) regulate immune activation <jats:italic>via<\/jats:italic> their roles in signal transduction of multiple classes of receptors. Here, we examined the effect of genetic inactivation of the hemopoietic cell\u2010restricted PI3K isoform p110\u03b4 on systemic cytokine and chemokine responses and allergic airway inflammation. We found that type\u20042 cytokine responses (IL\u20104, IL\u20105 and IL\u201013) are significantly decreased in p110\u03b4 mutants, whereas type\u20041 cytokine responses (IFN\u2010\u03b3 and CXCL10) were robust. Elevated IFN\u2010\u03b3 production during the primary response to ovalbumin (OVA) was associated with reduced production of the regulatory cytokine IL\u201010. IFN\u2010\u03b3 and IL\u201010 production normalized after secondary OVA immunization; however, type\u20042 cytokine production was persistently reduced. Type\u20042 cytokine\u2010dependent airway inflammation elicited by intranasal challenge with OVA was dramatically reduced, with reduced levels of eosinophil recruitment and mucus production observed in the lungs. Induction of respiratory hyper\u2010responsiveness to inhaled methacholine, a hallmark of asthma, was markedly attenuated in p110\u03b4\u2010inactivated mice. Adoptive transfer of OVA\u2010primed splenocytes from normal but not p110\u03b4\u2010inactivated mice could induce airway eosinophilia in naive, airway\u2010challenged recipient mice. These data demonstrate a novel functional role for p110\u03b4 signaling in induction of type\u20042 responses <jats:italic>in vivo<\/jats:italic> and may offer a new therapeutic target for Th2\u2010mediated airway disease.<\/jats:p>","DOI":"10.1002\/eji.200636401","type":"journal-article","created":{"date-parts":[[2007,1,19]],"date-time":"2007-01-19T09:51:27Z","timestamp":1169200287000},"page":"416-424","source":"Crossref","is-referenced-by-count":94,"title":["Role of the phosphoinositide 3\u2010kinase p110\u03b4 in generation of type\u20042 cytokine responses and allergic airway inflammation"],"prefix":"10.1002","volume":"37","author":[{"given":"Baher\u2004F.","family":"Nashed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monther","family":"Al\u2010Alwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh","family":"Srinivasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew\u2004J.","family":"Halayko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Okkenhaug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Vanhaesebroeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent\u2004T.","family":"HayGlass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron\u2004J.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,2]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104721"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1056"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5400.393"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5400.390"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.11.6615"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni825"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni768"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-001-2123-x"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.16.10963"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5455.1040"},{"key":"e_1_2_7_11_2","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1126\/science.1073560","article-title":"Impaired 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