title: Epithelial LTβR signaling controls the population size of the progenitors of medullary thymic epithelial cells in neonatal mice.
abstract: The establishment of T cell central tolerance critically relies on the development and maintenance of the medullary thymic epithelial cells (mTECs). Disrupted signaling of lymphotoxin beta receptor (LTβR) results in dramatically reduced mTEC population. However, whether LTβR directly or indirectly control mTECs remains undetermined; how LTβR controls this process also remain unclear. In this study, by utilizing K14-Cre × Ltbrfl/flconditional knockout (cKO) mice, we show that epithelial intrinsic LTβR was essential for the mTEC development postnatally. Mechanistically, LTβR did not directly impact the proliferation or survival of mTECs; the maturation of mTECs from MHC-IIloto MHC-IIhistage was also unaltered in the absence of LTβR; interestingly, the number of mTEC progenitors (Cld3,4hiSSEA-1+) was found significantly reduced in LTβR cKO mice at the neonatal stage, but not at E18.5. Consequently, epithelial deficiency of LTβR resulted in significant defect of thymic negative selection as demonstrated using OT-I and RIP-OVA transgenic mouse system. In summary, our study clarifies the epithelial intrinsic role of LTβR on mTEC development and function; more importantly, it reveals a previously unrecognized function of LTβR on the control of the size of mTEC progenitor population.
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Xia
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chai
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Caiwei
authors.initials: C
authors.lastname: Jin
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Boyang
authors.initials: B
authors.lastname: Ren
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000254:growth & development* / Q000378:metabolism
chemical_list: D053259:Lymphotoxin beta Receptor