TY - JOUR
T1 - Authors’ Reply to Letter to the Editor
T2 - Continued improvement to genetic diversity indicator for CBD
AU - Laikre, Linda
AU - Hohenlohe, Paul A.
AU - Allendorf, Fred W.
AU - Bertola, Laura D.
AU - Breed, Martin F.
AU - Bruford, Michael W.
AU - Funk, W. Chris
AU - Gajardo, Gonzalo
AU - González-Rodríguez, Antonio
AU - Grueber, Catherine E.
AU - Hedrick, Philip W.
AU - Heuertz, Myriam
AU - Hunter, Margaret E.
AU - Johannesson, Kerstin
AU - Liggins, Libby
AU - MacDonald, Anna J.
AU - Mergeay, Joachim
AU - Moharrek, Farideh
AU - O’Brien, David
AU - Ogden, Rob
AU - Orozco-terWengel, Pablo
AU - Palma-Silva, Clarisse
AU - Pierson, Jennifer
AU - Paz-Vinas, Ivan
AU - Russo, Isa Rita M.
AU - Ryman, Nils
AU - Segelbacher, Gernot
AU - Sjögren-Gulve, Per
AU - Waits, Lisette P.
AU - Vernesi, Cristiano
AU - Hoban, Sean
PY - 2021/8
Y1 - 2021/8
N2 - Chronic stimulation of CD8+ T cells triggers exhaustion, a distinct differentiation state with diminished effector function. Exhausted cells exist in multiple differentiation states, from stem-like progenitors that are the key mediators of the response to checkpoint blockade, through to terminally exhausted cells. Due to its clinical relevance, there is substantial interest in defining the pathways that control differentiation and maintenance of these subsets. Here, we show that chronic antigen induces the anergy-associated transcription factor EGR2 selectively within progenitor exhausted cells in both chronic LCMV and tumours. EGR2 enables terminal exhaustion and stabilizes the exhausted transcriptional state by both direct EGR2-dependent control of key exhaustion-associated genes, and indirect maintenance of the exhausted epigenetic state. We show that EGR2 is a regulator of exhaustion that epigenetically and transcriptionally maintains the differentiation competency of progenitor exhausted cells.
AB - Chronic stimulation of CD8+ T cells triggers exhaustion, a distinct differentiation state with diminished effector function. Exhausted cells exist in multiple differentiation states, from stem-like progenitors that are the key mediators of the response to checkpoint blockade, through to terminally exhausted cells. Due to its clinical relevance, there is substantial interest in defining the pathways that control differentiation and maintenance of these subsets. Here, we show that chronic antigen induces the anergy-associated transcription factor EGR2 selectively within progenitor exhausted cells in both chronic LCMV and tumours. EGR2 enables terminal exhaustion and stabilizes the exhausted transcriptional state by both direct EGR2-dependent control of key exhaustion-associated genes, and indirect maintenance of the exhausted epigenetic state. We show that EGR2 is a regulator of exhaustion that epigenetically and transcriptionally maintains the differentiation competency of progenitor exhausted cells.
UR - http://www.scopus.com/inward/record.url?scp=85105172416&partnerID=8YFLogxK
U2 - 10.1007/s10592-021-01359-w
DO - 10.1007/s10592-021-01359-w
M3 - Letter
SN - 1566-0621
VL - 22
SP - 533
EP - 536
JO - Conservation Genetics
JF - Conservation Genetics
IS - 4
ER -