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We show that Src homology region 2 domain-containing phosphatase-1 (SHP-1) is an important inhibitor of DC signaling, targeting multiple activation pathways. Downstream of TLR4, SHP-1 showed increased interaction with several proteins including IL-1R\u2013associated kinase-4, and modulated LPS signaling by inhibiting NF-\u03baB, AP-1, ERK, and JNK activity, while enhancing p38 activity. In addition, SHP-1 inhibited prosurvival signaling through AKT activation. Furthermore, SHP-1 inhibited CCR7 protein expression. Inhibiting SHP-1 in DCs enhanced proinflammatory cytokines, IL-6, IL-12, and IL-1\u03b2 production, promoted survival, and increased DC migration to draining lymph nodes. Administration of SHP-1\u2013inhibited DCs in vivo induced expansion of Ag-specific cytotoxic T cells and inhibited Foxp3+ regulatory T cell induction, resulting in an enhanced immune response against pre-established mouse melanoma and prostate tumors. Taken together, these data demonstrate that SHP-1 is an intrinsic global regulator of DC function, controlling many facets of T cell-mediated immune responses.<\/jats:p>","DOI":"10.4049\/jimmunol.1001675","type":"journal-article","created":{"date-parts":[[2011,2,26]],"date-time":"2011-02-26T05:53:36Z","timestamp":1298699616000},"page":"3934-3945","source":"Crossref","is-referenced-by-count":33,"title":["The Phosphatase Src Homology Region 2 Domain-Containing Phosphatase-1 Is an Intrinsic Central Regulator of Dendritic Cell Function"],"prefix":"10.1093","volume":"186","author":[{"given":"Indu R","family":"Ramachandran","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weitao","family":"Song","sequence":"additional","affiliation":[{"name":"Scott Department of Urology, Baylor College of Medicine , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Lapteva","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamatha","family":"Seethammagari","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin M","family":"Slawin","sequence":"additional","affiliation":[{"name":"Vanguard Urologic Institute , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine , Houston, TX 77030"},{"name":"Scott Department of Urology, Baylor College of Medicine , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan M","family":"Levitt","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine , Houston, TX 77030"},{"name":"Scott Department of Urology, Baylor College of Medicine , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,4,1]]},"reference":[{"key":"2025032411182607700_r1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/32588","article-title":"Dendritic cells and the control of immunity","volume":"392","author":"Banchereau","year":"1998","journal-title":"Nature"},{"key":"2025032411182607700_r2","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/nature06246","article-title":"Recognition of microorganisms and activation of the immune response","volume":"449","author":"Medzhitov","year":"2007","journal-title":"Nature"},{"key":"2025032411182607700_r3","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1046\/j.1365-2567.2001.01204.x","article-title":"In vivo maturation and migration of dendritic cells","volume":"102","author":"Flores-Romo","year":"2001","journal-title":"Immunology"},{"key":"2025032411182607700_r4","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1600-065X.2008.00718.x","article-title":"Inflammatory signals in dendritic cell activation and the induction of adaptive immunity","volume":"227","author":"Joffre","year":"2009","journal-title":"Immunol. 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