T cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice

Abstract IL-2Rα, in part, comprises the high affinity receptor for IL-2, a cytokine important in immune proliferation, activation, and regulation. IL-2Rα deficient mice (IL-2Rα-KO) develop systemic autoimmune disease and die from severe anemia between 18 and 80 days of age. These mice develop kineti...

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Autores principales:	Genevieve N. Mullins, Kristen M. Valentine, Mufadhal Al-Kuhlani, Dan Davini, Kirk D. C. Jensen, Katrina K. Hoyer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b5b676dfc164f7eb4056f8dcb9d590f
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spelling	oai:doaj.org-article:8b5b676dfc164f7eb4056f8dcb9d590f2021-12-02T13:34:00ZT cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice10.1038/s41598-020-78975-y2045-2322https://doaj.org/article/8b5b676dfc164f7eb4056f8dcb9d590f2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78975-yhttps://doaj.org/toc/2045-2322Abstract IL-2Rα, in part, comprises the high affinity receptor for IL-2, a cytokine important in immune proliferation, activation, and regulation. IL-2Rα deficient mice (IL-2Rα-KO) develop systemic autoimmune disease and die from severe anemia between 18 and 80 days of age. These mice develop kinetically distinct autoimmune progression, with approximately a quarter dying by 21 days of age and half dying after 30 days. This research aims to define immune parameters and cytokine signaling that distinguish cohorts of IL-2Rα-KO mice that develop early- versus late-stage autoimmune disease. To investigate these differences, we evaluated complete blood counts (CBC), antibody binding of RBCs, T cell numbers and activation, hematopoietic progenitor changes, and signaling kinetics, during autoimmune hemolytic anemia (AIHA) and bone marrow failure. We identified several alterations that, when combined, correlate to disease kinetics. Early onset disease correlates with anti-RBC antibodies, lower hematocrit, and reduced IL-7 signaling. CD8 regulatory T cells (Tregs) have enhanced apoptosis in early disease. Further, early and late end stage disease, while largely similar, had several differences suggesting distinct mechanisms drive autoimmune disease kinetics. Therefore, IL-2Rα-KO disease pathology rates, driven by T cell signaling, promote effector T cell activation and expansion and Treg dysfunction.Genevieve N. MullinsKristen M. ValentineMufadhal Al-KuhlaniDan DaviniKirk D. C. JensenKatrina K. HoyerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Genevieve N. Mullins Kristen M. Valentine Mufadhal Al-Kuhlani Dan Davini Kirk D. C. Jensen Katrina K. Hoyer T cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice
description	Abstract IL-2Rα, in part, comprises the high affinity receptor for IL-2, a cytokine important in immune proliferation, activation, and regulation. IL-2Rα deficient mice (IL-2Rα-KO) develop systemic autoimmune disease and die from severe anemia between 18 and 80 days of age. These mice develop kinetically distinct autoimmune progression, with approximately a quarter dying by 21 days of age and half dying after 30 days. This research aims to define immune parameters and cytokine signaling that distinguish cohorts of IL-2Rα-KO mice that develop early- versus late-stage autoimmune disease. To investigate these differences, we evaluated complete blood counts (CBC), antibody binding of RBCs, T cell numbers and activation, hematopoietic progenitor changes, and signaling kinetics, during autoimmune hemolytic anemia (AIHA) and bone marrow failure. We identified several alterations that, when combined, correlate to disease kinetics. Early onset disease correlates with anti-RBC antibodies, lower hematocrit, and reduced IL-7 signaling. CD8 regulatory T cells (Tregs) have enhanced apoptosis in early disease. Further, early and late end stage disease, while largely similar, had several differences suggesting distinct mechanisms drive autoimmune disease kinetics. Therefore, IL-2Rα-KO disease pathology rates, driven by T cell signaling, promote effector T cell activation and expansion and Treg dysfunction.
format	article
author	Genevieve N. Mullins Kristen M. Valentine Mufadhal Al-Kuhlani Dan Davini Kirk D. C. Jensen Katrina K. Hoyer
author_facet	Genevieve N. Mullins Kristen M. Valentine Mufadhal Al-Kuhlani Dan Davini Kirk D. C. Jensen Katrina K. Hoyer
author_sort	Genevieve N. Mullins
title	T cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice
title_short	T cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice
title_full	T cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice
title_fullStr	T cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice
title_full_unstemmed	T cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice
title_sort	t cell signaling and treg dysfunction correlate to disease kinetics in il-2rα-ko autoimmune mice
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/8b5b676dfc164f7eb4056f8dcb9d590f
work_keys_str_mv	AT genevievenmullins tcellsignalingandtregdysfunctioncorrelatetodiseasekineticsinil2rakoautoimmunemice AT kristenmvalentine tcellsignalingandtregdysfunctioncorrelatetodiseasekineticsinil2rakoautoimmunemice AT mufadhalalkuhlani tcellsignalingandtregdysfunctioncorrelatetodiseasekineticsinil2rakoautoimmunemice AT dandavini tcellsignalingandtregdysfunctioncorrelatetodiseasekineticsinil2rakoautoimmunemice AT kirkdcjensen tcellsignalingandtregdysfunctioncorrelatetodiseasekineticsinil2rakoautoimmunemice AT katrinakhoyer tcellsignalingandtregdysfunctioncorrelatetodiseasekineticsinil2rakoautoimmunemice
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T cell signaling and Treg dysfunction correlate to disease kinetics in IL-2Rα-KO autoimmune mice

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