Protection against autoimmunity is driven by thymic epithelial cell-mediated regulation of T reg development
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Protection against autoimmunity is driven by thymic epithelial cell-mediated regulation of T reg development. / Haftmann, Claudia; Zwicky, Pascale; Ingelfinger, Florian; Mair, Florian; Floess, Stefan; Riedel, René; Durek, Pawel; Spalinger, Marianne R.; Friebel, Ekaterina; Leung, Brian P.; Lutz, Mirjam; Puertas, Nicole; Amorim, Ana; Schärli, Stefanie; Becher, Benedict; Kisielow, Jan; Waisman, Ari; Mashreghi, Mir-Farzin; Huehn, Jochen; Becher, Burkhard.
In: SCI IMMUNOL, Vol. 6, No. 65, eabf3111, 19.11.2021.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Protection against autoimmunity is driven by thymic epithelial cell-mediated regulation of T reg development
AU - Haftmann, Claudia
AU - Zwicky, Pascale
AU - Ingelfinger, Florian
AU - Mair, Florian
AU - Floess, Stefan
AU - Riedel, René
AU - Durek, Pawel
AU - Spalinger, Marianne R.
AU - Friebel, Ekaterina
AU - Leung, Brian P.
AU - Lutz, Mirjam
AU - Puertas, Nicole
AU - Amorim, Ana
AU - Schärli, Stefanie
AU - Becher, Benedict
AU - Kisielow, Jan
AU - Waisman, Ari
AU - Mashreghi, Mir-Farzin
AU - Huehn, Jochen
AU - Becher, Burkhard
PY - 2021/11/19
Y1 - 2021/11/19
N2 - Medullary thymic epithelial cells (mTECs) are key antigen-presenting cells mediating T cell tolerance to prevent harmful autoimmunity. mTECs both negatively select self-reactive T cells and promote the development of thymic regulatory T cells (tTregs) that mediate peripheral tolerance. The relative importance of these two mechanisms of thymic education to prevent autoimmunity is unclear. We generated a mouse model to specifically target the development and function of mTECs by conditional ablation of the NF-B–inducing kinase (NIK) in the TEC com-partment. In contrast to germline-deficient NIK−/− mice, Foxn1CreNIKfl/fl mice rapidly developed fatal T cell–dependent multiorgan autoimmunity shortly after birth. Thymic transplantation and adoptive transfer experiments demon-strated that autoimmunity arises specifically from the emergence of dysfunctional tTregs. Thus, Treg function, rather than negative selection, enforces the protection of peripheral tissues from autoimmune attack.
AB - Medullary thymic epithelial cells (mTECs) are key antigen-presenting cells mediating T cell tolerance to prevent harmful autoimmunity. mTECs both negatively select self-reactive T cells and promote the development of thymic regulatory T cells (tTregs) that mediate peripheral tolerance. The relative importance of these two mechanisms of thymic education to prevent autoimmunity is unclear. We generated a mouse model to specifically target the development and function of mTECs by conditional ablation of the NF-B–inducing kinase (NIK) in the TEC com-partment. In contrast to germline-deficient NIK−/− mice, Foxn1CreNIKfl/fl mice rapidly developed fatal T cell–dependent multiorgan autoimmunity shortly after birth. Thymic transplantation and adoptive transfer experiments demon-strated that autoimmunity arises specifically from the emergence of dysfunctional tTregs. Thus, Treg function, rather than negative selection, enforces the protection of peripheral tissues from autoimmune attack.
U2 - 10.1126/sciimmunol.abf3111
DO - 10.1126/sciimmunol.abf3111
M3 - SCORING: Journal article
VL - 6
JO - SCI IMMUNOL
JF - SCI IMMUNOL
SN - 2470-9468
IS - 65
M1 - eabf3111
ER -
