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However, the regulatory mechanisms involved in GC differentiation and function during infection, particularly the role of immune cell\u2013IEC cross-talk, remain largely unknown. In this study, using Villin\u2206Ltbr conditional knockout mice, we demonstrate that LT\u03b2R, expressed on IECs, is required for GC hyperplasia and mucin 2 (MUC2) expression during Listeria infection for host defense but not homeostatic maintenance in the naive state. Analysis of single gene-deficient mice revealed that the ligand lymphotoxin (LT), but not LIGHT, and type 3 innate lymphoid cells (ILC3s), but not conventional T cells, are required for MUC2-dependent Listeria control. Conditional deficiency of LT in ILC3s further confirmed the importance of LT signals derived from ILC3s. Lack of ILC3-derived LT or IEC-derived LT\u03b2R resulted in the defective expression of genes related to GC differentiation but was not correlated with IEC proliferation and cell death, which were found to be normal by Ki-67 and Annexin V staining. In addition, the alternative NF-\u03baB signaling pathway (involving RelB) in IECs was found to be required for the expression of GC differentiation-related genes and Muc2 and required for the anti-Listeria response. Therefore, our data together suggest a previously unrecognized ILC3\u2013IEC interaction and LT\u2013LT\u03b2R\u2013RelB signaling axis governing GC differentiation and function during Listeria infection for host defense.<\/jats:p>","DOI":"10.4049\/jimmunol.2000197","type":"journal-article","created":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T23:12:37Z","timestamp":1593213157000},"page":"853-863","source":"Crossref","is-referenced-by-count":19,"title":["Type 3 Innate Lymphoid Cells Direct Goblet Cell Differentiation via the LT\u2013LT\u03b2R Pathway during <i>Listeria<\/i> Infection"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1519-3947","authenticated-orcid":false,"given":"Yaya","family":"Pian","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0938-8166","authenticated-orcid":false,"given":"Qian","family":"Chai","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyang","family":"Ren","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"College of Life Sciences, University of Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"College of Life Sciences, University of Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Lv","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Qiu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences , Shanghai 200031 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2001-2669","authenticated-orcid":false,"given":"Mingzhao","family":"Zhu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"College of Life Sciences, University of Chinese Academy of Sciences , Beijing 100049 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,1]]},"reference":[{"key":"2025030417504529000_r1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.it.2011.04.003","article-title":"The intestinal epithelial barrier in the control of homeostasis and immunity","volume":"32","author":"Rescigno","year":"2011","journal-title":"Trends Immunol."},{"key":"2025030417504529000_r2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nri3608","article-title":"Intestinal epithelial cells: regulators of barrier function and immune homeostasis","volume":"14","author":"Peterson","year":"2014","journal-title":"Nat. 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