title: Lymphotoxin β receptor regulates the development of CCL21-expressing subset of postnatal medullary thymic epithelial cells.
abstract: Medullary thymic epithelial cells (mTECs) play a pivotal role in the establishment of self-tolerance in T cells by ectopically expressing various tissue-restricted self-Ags and by chemoattracting developing thymocytes. The nuclear protein Aire expressed by mTECs contributes to the promiscuous expression of self-Ags, whereas CCR7-ligand (CCR7L) chemokines expressed by mTECs are responsible for the attraction of positively selected thymocytes. It is known that lymphotoxin signals from the positively selected thymocytes preferentially promote the expression of CCR7L rather than Aire in postnatal mTECs. However, it is unknown how lymphotoxin signals differentially regulate the expression of CCR7L and Aire in mTECs and whether CCR7L-expressing mTECs and Aire-expressing mTECs are distinct populations. In this study, we show that the majority of postnatal mTECs that express CCL21, a CCR7L chemokine, represent an mTEC subpopulation distinct from the Aire-expressing mTEC subpopulation. Interestingly, the development of CCL21-expressing mTECs, but not Aire-expressing mTECs, is impaired in mice deficient in the lymphotoxin β receptor. These results indicate that postnatal mTECs consist of heterogeneous subsets that differ in the expression of CCL21 and Aire, and that lymphotoxin β receptor regulates the development of the CCL21-expressing subset rather than the Aire-expressing subset of postnatal mTECs.
authors.affiliation: Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Enkhsaikhan
authors.initials: E
authors.lastname: Lkhagvasuren
authors.forename: Mie
authors.initials: M
authors.lastname: Sakata
authors.forename: Izumi
authors.initials: I
authors.lastname: Ohigashi
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Takahama
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D054421:Chemokine CCL21 / Q000096:biosynthesis*; D004847:Epithelial Cells; D053259:Lymphotoxin beta Receptor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054400:Receptors, CCR7; D015398:Signal Transduction; D013950:Thymus Gland / Q000378:metabolism*; D014157:Transcription Factors; D000096927:AIRE Protein
chemical_list: D054421:Chemokine CCL21; D053259:Lymphotoxin beta Receptor; D054400:Receptors, CCR7; D014157:Transcription Factors; D000096927:AIRE Protein