TY - JOUR
T1 - Hobit and Blimp-1 instruct the differentiation of iNKT cells into resident-phenotype lymphocytes after lineage commitment
AU - Kragten, Natasja A. M.
AU - Taggenbrock, Renske L. RE
AU - Parga Vidal, Loreto
AU - van Lier, Rene A. W.
AU - Stark, Regina
AU - van Gisbergen, Klaas P. JM
N1 - Funding Information: We would like to thank the members of the van Gisbergen Laboratory and the department of Hematopoiesis for fruitful discussions. N.A.M.K., K.P.J.M.v.G., and L.P.V. were supported by a fellowship of the Landsteiner Foundation of Blood Transfusion Research. R.S. was supported by Veni grant 016.186.116 from the Netherlands Organization for Scientific Research (NWO). Publisher Copyright: © 2022 Wiley-VCH GmbH
PY - 2022/3
Y1 - 2022/3
N2 - iNKT cells are CD1d-restricted T cells that play a pro-inflammatory or regulatory role in infectious and autoimmune diseases. Thymic precursors of iNKT cells eventually develop into distinct iNKT1, iNKT2, and iNKT17 lineages in the periphery. It remains unclear whether iNKT cells retain developmental potential after lineage commitment. iNKT cells acquire a similar phenotype as tissue-resident memory T cells, suggesting that they also differentiate along a trajectory that enables them to persist in peripheral tissues. Here, we addressed whether lineage commitment and memory differentiation are parallel or sequential developmental programs of iNKT cells. We defined three subsets of peripheral iNKT cells using CD62L and CD69 expression that separate central, effector, and resident memory phenotype cells. The majority of iNKT1 cells displayed a resident phenotype in contrast to iNKT2 and iNKT17 cells. The transcription factor Hobit, which is upregulated in iNKT cells, plays an essential role in their development together with its homolog Blimp-1. Hobit and Blimp-1 instructed the differentiation of central memory iNKT cells into resident memory iNKT cells, but did not impact commitment into iNKT1, iNKT2, or iNKT17 lineages. Thus, we conclude that memory differentiation and the establishment of residency occur after lineage commitment through a Hobit and Blimp-1-driven transcriptional program.
AB - iNKT cells are CD1d-restricted T cells that play a pro-inflammatory or regulatory role in infectious and autoimmune diseases. Thymic precursors of iNKT cells eventually develop into distinct iNKT1, iNKT2, and iNKT17 lineages in the periphery. It remains unclear whether iNKT cells retain developmental potential after lineage commitment. iNKT cells acquire a similar phenotype as tissue-resident memory T cells, suggesting that they also differentiate along a trajectory that enables them to persist in peripheral tissues. Here, we addressed whether lineage commitment and memory differentiation are parallel or sequential developmental programs of iNKT cells. We defined three subsets of peripheral iNKT cells using CD62L and CD69 expression that separate central, effector, and resident memory phenotype cells. The majority of iNKT1 cells displayed a resident phenotype in contrast to iNKT2 and iNKT17 cells. The transcription factor Hobit, which is upregulated in iNKT cells, plays an essential role in their development together with its homolog Blimp-1. Hobit and Blimp-1 instructed the differentiation of central memory iNKT cells into resident memory iNKT cells, but did not impact commitment into iNKT1, iNKT2, or iNKT17 lineages. Thus, we conclude that memory differentiation and the establishment of residency occur after lineage commitment through a Hobit and Blimp-1-driven transcriptional program.
KW - Blimp-1
KW - Differentiation
KW - Hobit
KW - Lineage commitment
KW - Tissue residency
KW - iNKT cells
UR - http://www.scopus.com/inward/record.url?scp=85122613207&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/eji.202149360
DO - https://doi.org/10.1002/eji.202149360
M3 - Article
C2 - 34897659
SN - 0014-2980
VL - 52
SP - 389
EP - 403
JO - European journal of immunology
JF - European journal of immunology
IS - 3
ER -