{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:03:43Z","timestamp":1784610223452,"version":"3.55.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Organic dust exposures, particularly in occupational settings, induce airway inflammation and contribute to the development and progression of chronic lung disease and impaired tissue regeneration. Interleukin-22 (IL-22) is a pleiotropic cytokine recognized for maintaining epithelial barrier integrity and promoting tissue repair; however, its regulation in lung myeloid cells, particularly macrophages, remains poorly understood. Toll-like receptor 2 (TLR2), a pattern recognition receptor highly expressed on lung macrophages, recognizes bacterial components abundant in organic dust and drives inflammatory signaling. We investigated the mechanistic role of TLR2 signaling in regulating IL-22 production by lung macrophages following exposure to microbial-enriched agricultural organic dust extract (DE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An immortalized lung macrophage cell line (MH-S) was stimulated with selective Toll-like receptor agonists and pharmacologic inhibitors to determine the contribution of individual TLR pathways to IL-22 production. To examine the role of TLR2\n                      <jats:italic>in vivo<\/jats:italic>\n                      , wild-type (WT) and TLR2-deficient (\n                      <jats:italic>tlr2-\/-<\/jats:italic>\n                      ) mice were exposed to DE repeatedly for two weeks. IL-22 expression and macrophage localization were evaluated using RNAscope in situ hybridization and immunofluorescence analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TLR2 stimulation preferentially induced IL-22 production compared with other TLR pathways while simultaneously coordinating pro-inflammatory cytokine responses. Activation of the TLR2\/1 heterodimer, but not TLR2\/6, significantly increased IL-22 production, indicating pathway-specific regulation of reparative signaling. In vivo, repeated DE exposure resulted in significantly reduced pulmonary IL-22 expression in\n                      <jats:italic>tlr2-\/-<\/jats:italic>\n                      mice compared with WT controls. Furthermore,\n                      <jats:italic>tlr2-\/-<\/jats:italic>\n                      lungs exhibited fewer IL-22\n                      <jats:sup>+<\/jats:sup>\n                      CD68\n                      <jats:sup>+<\/jats:sup>\n                      cells, an overall reduction in macrophage numbers, and a significant decrease in the proportion of CD68+ macrophages expressing IL-22, suggesting that TLR2 is required for both macrophage accumulation and IL-22 production during dust-induced lung injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion\/Conclusion<\/jats:title>\n                    <jats:p>These findings identify TLR2 as a critical regulator of IL-22-mediated reparative programming in lung macrophages following organic dust exposure. Our study reveals a previously unrecognized link between innate immune sensing and epithelial repair pathways, providing mechanistic insight into how TLR2 promotes tissue restoration after environmental lung injury. Targeting the TLR2-IL-22 axis may represent a promising therapeutic strategy for mitigating occupational dust-induced lung damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1880821","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:19:40Z","timestamp":1784607580000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Toll-like receptor 2 coordinates induction of IL-22 in lung macrophages following organic dust-induced inflammation"],"prefix":"10.3389","volume":"17","author":[{"given":"Emmanuel O.","family":"Oyewole","sequence":"first","affiliation":[{"name":"Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University","place":["Fort Collins, CO, United States"]},{"name":"Toxicology Graduate Program, Colorado State University","place":["Fort Collins, CO, United 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