PMID- 34440780 OWN - NLM STAT- MEDLINE DCOM- 20211115 LR - 20221207 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 10 IP - 8 DP - 2021 Aug 6 TI - Human Lung-Resident Macrophages Express and Are Targets of Thymic Stromal Lymphopoietin in the Tumor Microenvironment. LID - 10.3390/cells10082012 [doi] LID - 2012 AB - Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine highly expressed by epithelial cells and several innate and adaptive immune cells. TSLP exerts its biological effects by binding to a heterodimeric complex composed of TSLP receptor (TSLPR) and IL-7Ralpha. In humans, there are two TSLP isoforms: the short form (sfTSLP), constitutively expressed, and the long form (lfTSLP), which is upregulated in inflammation. TSLP has been implicated in the induction and progression of several experimental and human cancers. Primary human lung macrophages (HLMs), monocyte-derived macrophages (MDMs), and peripheral blood monocytes consitutively expressed sfTSLP mRNA. Incubation of HLMs, MDMs, and monocytes with lipopolysaccharide (LPS) or IL-4, but not with IL-13, induced TSLP release from HLMs. LPS, but not IL-4 or IL-13, induced CXCL8 release from HLMs. LPS, IL-4 alone or in combination with IL-13, induced the expression of lfTSLP, but not of sfTSLP from HLMs. Preincubation of HLMs with IL-4, alone or in combination with IL-13, but not IL-13 alone, synergistically enhanced TSLP release from LPS-activated macrophages. By contrast, IL-4, alone or in combination with IL-13, inhibited LPS-induced CXCL8 release from HLMs. Immunoreactive TSLP was detected in lysates of HLMs, MDMs, and monocytes. Incubation of HLMs with TSLP induced the release of proinflammatory (TNF-alpha), angiogenic (VEGF-A, angiopoietin 2), and lymphangiogenic (VEGF-C) factors. TSLP, TSLPR, and IL-7Ralpha were expressed in intratumoral and peritumoral areas of human lung cancer. sfTSLP and lfTSLP mRNAs were differentially expressed in peritumoral and intratumoral lung cancer tissues. The TSLP system, expressed in HLMs, MDMs, and monocytes, could play a role in chronic inflammatory disorders including lung cancer. FAU - Braile, Mariantonia AU - Braile M AD - Center for Basic and Clinical Immunology Research (CISI), Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy. AD - WAO Center of Excellence, 80131 Naples, Italy. FAU - Fiorelli, Alfonso AU - Fiorelli A AUID- ORCID: 0000-0002-0628-613X AD - Department of Translational Medical and Surgical Science, University of Campania Luigi Vanvitelli, 80131 Naples, Italy. FAU - Sorriento, Daniela AU - Sorriento D AUID- ORCID: 0000-0002-1599-4509 AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy. FAU - Di Crescenzo, Rosa Maria AU - Di Crescenzo RM AD - Department of Translational Medical and Surgical Science, University of Campania Luigi Vanvitelli, 80131 Naples, Italy. FAU - Galdiero, Maria Rosaria AU - Galdiero MR AD - Center for Basic and Clinical Immunology Research (CISI), Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy. AD - WAO Center of Excellence, 80131 Naples, Italy. AD - Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy. FAU - Marone, Gianni AU - Marone G AUID- ORCID: 0000-0002-9849-4701 AD - Center for Basic and Clinical Immunology Research (CISI), Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy. AD - WAO Center of Excellence, 80131 Naples, Italy. AD - Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy. FAU - Santini, Mario AU - Santini M AUID- ORCID: 0000-0003-1162-7805 AD - Department of Translational Medical and Surgical Science, University of Campania Luigi Vanvitelli, 80131 Naples, Italy. FAU - Varricchi, Gilda AU - Varricchi G AUID- ORCID: 0000-0002-9285-4657 AD - Center for Basic and Clinical Immunology Research (CISI), Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy. AD - WAO Center of Excellence, 80131 Naples, Italy. AD - Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy. FAU - Loffredo, Stefania AU - Loffredo S AUID- ORCID: 0000-0002-5871-1898 AD - Center for Basic and Clinical Immunology Research (CISI), Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy. AD - WAO Center of Excellence, 80131 Naples, Italy. AD - Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131 Naples, Italy. LA - eng GR - Not available/CISI- LAB PROJECT (UNIVERSITY OF NAPLES FEDERICO II)/ GR - Not available/TIMING PROJECT (REGIONE CAMPANIA)/ GR - Not available/CAMPANIA BIOSCIENCE (REGIONE CAMPANIA)/ GR - M8Y MR_8005/MIUR PRIN 2017/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210806 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Angiogenic Proteins) RN - 0 (CRLF2 protein, human) RN - 0 (Cytokines) RN - 0 (IL7R protein, human) RN - 0 (Interleukin-7 Receptor alpha Subunit) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, Cytokine) RN - GT0IL38SP4 (Thymic Stromal Lymphopoietin) SB - IM MH - Adenocarcinoma of Lung/genetics/immunology/*metabolism/pathology MH - Aged MH - Angiogenic Proteins/metabolism MH - Cells, Cultured MH - Cytokines/genetics/*metabolism/pharmacology MH - Female MH - Humans MH - Interleukin-7 Receptor alpha Subunit/genetics/metabolism MH - Lipopolysaccharides/pharmacology MH - Lung Neoplasms/genetics/immunology/*metabolism/pathology MH - Lymphangiogenesis MH - *Macrophage Activation/drug effects MH - Macrophages, Alveolar/drug effects/immunology/*metabolism MH - Male MH - Middle Aged MH - Neovascularization, Pathologic MH - Receptors, Cytokine/genetics/metabolism MH - Signal Transduction MH - *Tumor Microenvironment MH - Thymic Stromal Lymphopoietin PMC - PMC8392295 OTO - NOTNLM OT - TSLP isoforms OT - angiogenesis OT - lung cancer OT - lymphangiogenesis OT - macrophages OT - monocyte-derived macrophages OT - monocytes OT - thymic stromal lymphopoietin OT - tumor microenvironment COIS- The authors declare no conflict of interest. EDAT- 2021/08/28 06:00 MHDA- 2021/11/16 06:00 PMCR- 2021/08/06 CRDT- 2021/08/27 01:08 PHST- 2021/07/06 00:00 [received] PHST- 2021/08/02 00:00 [revised] PHST- 2021/08/03 00:00 [accepted] PHST- 2021/08/27 01:08 [entrez] PHST- 2021/08/28 06:00 [pubmed] PHST- 2021/11/16 06:00 [medline] PHST- 2021/08/06 00:00 [pmc-release] AID - cells10082012 [pii] AID - cells-10-02012 [pii] AID - 10.3390/cells10082012 [doi] PST - epublish SO - Cells. 2021 Aug 6;10(8):2012. doi: 10.3390/cells10082012.