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Micro RNA miR‐181a/b‐1 controls MAIT cell development
Author(s) -
Winter Samantha J,
KunzeSchumacher Heike,
Imelmann Esther,
Grewers Zoe,
Osthues Tabea,
Krueger Andreas
Publication year - 2019
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12211
Subject(s) - microrna , chemistry , cell , rna , microbiology and biotechnology , biology , biochemistry , gene
Abstract Mucosal‐associated invariant T (MAIT) cells constitute a major fraction of innate‐like T cells in humans with critical roles in defense against microbial pathogens and in maintaining mucosal integrity. However, the molecular mechanisms underlying MAIT cell development remain largely elusive. Here we investigated the role of miR‐181a/b‐1, a pair of micro RNA s that serve as rheostat of TCR signal strength, in this process. Loss of miR‐181a/b‐1 in mice resulted in a profound arrest in early MAIT cell development. As a consequence, in the absence of miR‐181a/b‐1, thymic MAIT cells failed to acquire functional maturity based on expression of transcription factors PLZF , T‐bet and ROR γt. Temporal analysis of development using a molecular timer in combination with loss of miR‐181a/b‐1 revealed that MAIT cells complete functional maturation in the periphery and indicates that functionally mature MAIT cells in the thymus are long‐term resident cells. Thus, our study provides insight into the dynamics of MAIT cell development in vivo . Of note, deletion of miR‐181a/b‐1 alone completely mirrored loss of all mi RNA s.