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The surveillance of viral infections by the unconventional Type I NKT cell


Review

. 2024 Sep 17:15:1472854.


doi: 10.3389/fimmu.2024.1472854.


eCollection 2024.

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Review

Varshini Rajashekar et al.


Front Immunol.


.

Abstract

Type I NKT cells, also known as Invariant Natural Killer T (iNKT) cells, are a subpopulation of unconventional, innate-like T (ILT) cells which can proficiently influence downstream immune effector functions. Type I NKT cells express a semi-invariant αβ T cell receptor (TCR) that recognises lipid-based ligands specifically presented by the non-classical cluster of differentiation (CD1) protein d (CD1d) molecule. Due to their potent immunomodulatory functional capacity, type I NKT cells are being increasingly considered in prophylactic and therapeutic approaches towards various diseases, including as vaccine-adjuvants. As viruses do not encode lipid synthesis, it is surprising that many studies have shown that some viruses can directly impede type I NKT activation through downregulating CD1d expression. Therefore, in order to harness type I NKT cells for potential anti-viral therapeutic uses, it is critical that we fully appreciate how the CD1d-iNKT cell axis interacts with viral immunity. In this review, we examine clinical findings that underpin the importance of type I NKT cell function in viral infections. This review also explores how certain viruses employ immunoevasive mechanisms and directly encode functions to target CD1d expression and type I NKT cell function. Overall, we suggest that the CD1d-iNKT cell axis may hold greater gravity within viral infections than what was previously appreciated.


Keywords:

CD1d-iNKT cell axis; type I NKT cell; type I iNKT cell function; unconventional innate-like T cell; viral infections.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

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