title: NFIL3 Expression Distinguishes Tissue-Resident NK Cells and Conventional NK-like Cells in the Mouse Submandibular Glands.
abstract: The submandibular salivary gland (SMG), a major site of persistent infection for many viruses, contains a large NK cell population. Using NFIL3-deficient mice, PLZF reporter/fate mapping mice, and mixed bone marrow chimeras, we identified two distinct populations of NK cells in the SMG. Although phenotypically unique, the main population relies on NFIL3, but not PLZF, for development and, therefore, is developmentally similar to the conventional NK cell subset. In contrast, we found that approximately one quarter of the SMG NK cells develop independently of NFIL3. Interestingly, NFIL3-independent SMG tissue-resident NK (trNK) cells are developmentally distinct from liver trNK cells. We also demonstrated that the SMG NK cell hyporesponsive phenotype during murine CMV infection is tissue specific and not cell intrinsic. In contrast, NFIL3-independent SMG trNK cells are intrinsically hyporesponsive. Altogether, our data show that the SMG tissue environment shapes a unique repertoire of NK-like cells with distinct phenotypes.
authors: Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912; and.
authors: Timothy K
authors: TK
authors: Erick
authors: Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912; and.
authors: Courtney K
authors: CK
authors: Anderson
authors: Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912; and.
authors: Emma C
authors: EC
authors: Reilly
authors: Liver Research Center, Rhode Island Hospital and the Department of Medicine, Warren Alpert Medical School at Brown University, Providence, RI 02912.
authors: Jack R
authors: 0000-0003-1731-624X
authors: JR
authors: Wands
authors: Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912; and Laurent_Brossay@brown.edu.
authors: Laurent
authors: 0000-0002-7497-8488
authors: L
authors: Brossay
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology; D005434:Flow Cytometry; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000276:immunology; D051379:Mice; D010641:Phenotype; D013363:Submandibular Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C497441:Nfil3 protein, mouse