{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:35:47Z","timestamp":1768509347588,"version":"3.49.0"},"posted":{"date-parts":[[2023,11,5]]},"group-title":"Immunology","reference-count":66,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The protein basic helix-loop-helix family member e40 (BHLHE40) is a transcription factor recently emerged as a key regulator of host immunity to infections, autoimmune diseases and cancer. In this study, we investigated the role of\n                  <jats:italic>Bhlhe40<\/jats:italic>\n                  in protective T cell responses to the intracellular bacterium\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  in the female reproductive tract (FRT). Mice deficient in\n                  <jats:italic>Bhlhe40<\/jats:italic>\n                  exhibited severe defects in their ability to control\n                  <jats:italic>Chlamydia muridarum<\/jats:italic>\n                  shedding from the FRT. The heightened bacterial burdens in\n                  <jats:italic>\n                    Bhlhe40\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  mice correlated with a marked increase in IL-10-producing T regulatory type 1 (Tr1) cells and decreased polyfunctional CD4 T cells co-producing IFN-\u03b3, IL-17A and GM-CSF. Genetic ablation of IL-10 or functional blockade of IL-10R increased CD4 T cell polyfunctionality and partially rescued the defects in bacterial control in\n                  <jats:italic>\n                    Bhlhe40\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  mice. Using single-cell RNA sequencing coupled with TCR profiling, we detected a significant enrichment of stem-like T cell signatures in\n                  <jats:italic>Bhlhe40<\/jats:italic>\n                  -deficient CD4 T cells, whereas WT CD4 T cells were further down on the differentiation trajectory with distinct effector functions beyond IFN-\u03b3 production by Th1 cells. Altogether, we identified\n                  <jats:italic>Bhlhe40<\/jats:italic>\n                  as a key molecular driver of CD4 T cell differentiation and polyfunctional responses in the FRT against\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2023.11.02.565369","type":"posted-content","created":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T16:35:16Z","timestamp":1699202116000},"source":"Crossref","is-referenced-by-count":0,"title":["BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract against\n                  <i>Chlamydia<\/i>"],"prefix":"10.64898","author":[{"given":"Miguel A. 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