{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T16:53:20Z","timestamp":1775580800600,"version":"3.50.1"},"posted":{"date-parts":[[2024,1,7]]},"group-title":"Immunology","reference-count":50,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,1,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Humoral immune responses within the gut play diverse roles including pathogen clearance during enteric infections, maintaining tolerance, and facilitating the assemblage and stability of the gut microbiota. How these humoral immune responses are initiated and contribute to these processes are well studied. However, the signals promoting the expansion of these responses and their rapid mobilization to the gut mucosa are less well understood. Intestinal goblet cells form goblet cell-associated antigen passages (GAPs) to deliver luminal antigens to the underlying immune system and facilitate tolerance. GAPs are rapidly inhibited during enteric infection to prevent inflammatory responses to innocuous luminal antigens. Here we interrogate GAP inhibition as a key physiological response required for effective humoral immunity. Independent of infection, GAP inhibition resulted in enrichment of transcripts representing B cell recruitment, expansion, and differentiation into plasma cells in the small intestine (SI), which were confirmed by flow cytometry and ELISpot assays. Further we observed an expansion of isolated lymphoid follicles within the SI, as well as expansion of plasma cells in the bone marrow upon GAP inhibition. S1PR1-induced blockade of leukocyte trafficking during GAP inhibition resulted in a blunting of SI plasma cell expansion, suggesting that mobilization of plasma cells from the bone marrow contributes to their expansion in the gut. However, luminal IgA secretion was only observed in the presence of\n                  <jats:italic>S. typhimurium<\/jats:italic>\n                  infection, suggesting that although GAP inhibition mobilizes a mucosal humoral immune response, a second signal is required for full effector function. Overriding GAP inhibition during enteric infection abrogated the expansion of laminar propria IgA+ plasma cells. We conclude that GAP inhibition is a required physiological response for efficiently mobilizing mucosal humoral immunity in response to enteric infection.\n                <\/jats:p>","DOI":"10.1101\/2024.01.06.573891","type":"posted-content","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T16:10:50Z","timestamp":1704730250000},"source":"Crossref","is-referenced-by-count":1,"title":["Small Intestinal Goblet Cells Control Humoral Immune Responses and Mobilization During Enteric Infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8562-8205","authenticated-orcid":false,"given":"Devesha H.","family":"Kulkarni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khushi","family":"Talati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth L.","family":"Joyce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hrishi","family":"Kousik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalia L.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandria N.","family":"Floyd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitaly","family":"Vavrinyuk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibianna","family":"Barrios","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sreeram","family":"Udayan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keely","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vini","family":"John","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chyi-Song","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodney D.","family":"Newberry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024010922065636000_2024.01.06.573891v1.1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070602"},{"key":"2024010922065636000_2024.01.06.573891v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10434"},{"key":"2024010922065636000_2024.01.06.573891v1.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1237910"},{"key":"2024010922065636000_2024.01.06.573891v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nri2710"},{"key":"2024010922065636000_2024.01.06.573891v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2007.6"},{"key":"2024010922065636000_2024.01.06.573891v1.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.1091334"},{"key":"2024010922065636000_2024.01.06.573891v1.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-009-0174-3"},{"key":"2024010922065636000_2024.01.06.573891v1.8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901838"},{"key":"2024010922065636000_2024.01.06.573891v1.9","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.61.12.5271-5278.1993"},{"key":"2024010922065636000_2024.01.06.573891v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.05.014"},{"key":"2024010922065636000_2024.01.06.573891v1.11","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1309.006"},{"key":"2024010922065636000_2024.01.06.573891v1.12","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5474.2222"},{"key":"2024010922065636000_2024.01.06.573891v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.59"},{"key":"2024010922065636000_2024.01.06.573891v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature10863"},{"key":"2024010922065636000_2024.01.06.573891v1.15","unstructured":"Kulkarni, D.H. , et al., Goblet cell associated antigen passages support the induction and maintenance of oral tolerance. Mucosal Immunol, 2019."},{"key":"2024010922065636000_2024.01.06.573891v1.16","doi-asserted-by":"crossref","unstructured":"Gustafsson, J.K. , et al., Intestinal goblet cells sample and deliver lumenal antigens by regulated endocytic uptake and transcytosis. Elife, 2021. 10.","DOI":"10.7554\/eLife.67292"},{"issue":"1","key":"2024010922065636000_2024.01.06.573891v1.17","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/mi.2014.58","article-title":"Microbial sensing by goblet cells controls immune surveillance of luminal antigens in the colon","volume":"8","year":"2015","journal-title":"Mucosal Immunology"},{"key":"2024010922065636000_2024.01.06.573891v1.18","doi-asserted-by":"crossref","unstructured":"Kulkarni, D.H. , et al., Goblet cell associated antigen passages are inhibited during Salmonella typhimurium infection to prevent pathogen dissemination and limit responses to dietary antigens. Mucosal Immunol, 2018.","DOI":"10.1038\/s41385-018-0007-6"},{"issue":"1","key":"2024010922065636000_2024.01.06.573891v1.19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/imr.12980","article-title":"Fantastic IgA plasma cells and where to find them","volume":"303","year":"2021","journal-title":"Immunol Rev"},{"key":"2024010922065636000_2024.01.06.573891v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/nature10698"},{"key":"2024010922065636000_2024.01.06.573891v1.21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.11.5475"},{"key":"2024010922065636000_2024.01.06.573891v1.22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.9.5720"},{"key":"2024010922065636000_2024.01.06.573891v1.23","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090723"},{"key":"2024010922065636000_2024.01.06.573891v1.24","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4933-8-1"},{"issue":"8","key":"2024010922065636000_2024.01.06.573891v1.25","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.it.2021.06.003","article-title":"CD4(+) T cells that help B cells - a proposal for uniform nomenclature","volume":"42","year":"2021","journal-title":"Trends Immunol"},{"key":"2024010922065636000_2024.01.06.573891v1.26","doi-asserted-by":"crossref","unstructured":"Landuyt, A.E. , et al., ICOS ligand and IL-10 synergize to promote host-microbiota mutualism. Proc Natl Acad Sci U S A, 2021. 118(13).","DOI":"10.1073\/pnas.2018278118"},{"key":"2024010922065636000_2024.01.06.573891v1.27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801266"},{"key":"2024010922065636000_2024.01.06.573891v1.28","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20032000"},{"key":"2024010922065636000_2024.01.06.573891v1.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511305103"},{"key":"2024010922065636000_2024.01.06.573891v1.30","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-635805"},{"key":"2024010922065636000_2024.01.06.573891v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/40540"},{"key":"2024010922065636000_2024.01.06.573891v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80541-5"},{"key":"2024010922065636000_2024.01.06.573891v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.38"},{"key":"2024010922065636000_2024.01.06.573891v1.34","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140457"},{"key":"2024010922065636000_2024.01.06.573891v1.35","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031104"},{"issue":"1","key":"2024010922065636000_2024.01.06.573891v1.36","first-page":"11","article-title":"Role of sphingosine 1-phosphate receptor type 1 in lymphocyte egress from secondary lymphoid tissues and thymus","volume":"3","year":"2006","journal-title":"Cell Mol Immunol"},{"key":"2024010922065636000_2024.01.06.573891v1.37","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200176200"},{"issue":"2","key":"2024010922065636000_2024.01.06.573891v1.38","doi-asserted-by":"crossref","first-page":"677","DOI":"10.4049\/jimmunol.162.2.677","article-title":"Thymic stromal lymphopoietin: a cytokine that promotes the development of IgM+ B cells in vitro and signals via a novel mechanism","volume":"162","year":"1999","journal-title":"J Immunol"},{"key":"2024010922065636000_2024.01.06.573891v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.09.004"},{"key":"2024010922065636000_2024.01.06.573891v1.40","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-309059"},{"key":"2024010922065636000_2024.01.06.573891v1.41","doi-asserted-by":"crossref","unstructured":"Knoop, K.A. , et al., Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria. Sci Immunol, 2017. 2(18).","DOI":"10.1126\/sciimmunol.aao1314"},{"key":"2024010922065636000_2024.01.06.573891v1.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1912022117"},{"key":"2024010922065636000_2024.01.06.573891v1.43","doi-asserted-by":"crossref","unstructured":"Knoop, K.A. , et al., Synchronization of mothers and offspring promotes tolerance and limits allergy. JCI Insight, 2020. 5(15).","DOI":"10.1172\/jci.insight.137943"},{"key":"2024010922065636000_2024.01.06.573891v1.44","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.12.2381"},{"key":"2024010922065636000_2024.01.06.573891v1.45","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101715"},{"key":"2024010922065636000_2024.01.06.573891v1.46","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat7186"},{"key":"2024010922065636000_2024.01.06.573891v1.47","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3843-09.2010"},{"key":"2024010922065636000_2024.01.06.573891v1.48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911579106"},{"key":"2024010922065636000_2024.01.06.573891v1.49","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.21.6056-6059.2002"},{"key":"2024010922065636000_2024.01.06.573891v1.50","doi-asserted-by":"publisher","DOI":"10.2144\/000112514"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.01.06.573891","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:45:49Z","timestamp":1768455949000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.01.06.573891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,7]]},"references-count":50,"URL":"https:\/\/doi.org\/10.1101\/2024.01.06.573891","relation":{},"subject":[],"published":{"date-parts":[[2024,1,7]]},"subtype":"preprint"}}