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Cited by 17T-cell and B-cell ImmunologyNeuroinflammation and Neurodegeneration MechanismsMultiple Sclerosis Research Studies

The immune system in neurological diseases: what innate‐like T cells have to say

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Wyatt-Johnson, Season K., Afify, Reham, Brutkiewicz, Randy R.·2024·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2024.02.003PMC PMC10999338
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Abstract

The immune system classically consists of 2 lines of defense, innate and adaptive, both of which interact with one another effectively to protect us against any pathogenic threats. Importantly, there is a diverse subset of cells known as innate-like T cells that act as a bridge between the innate and adaptive immune systems and are pivotal players in eliciting inflammatory immune responses. A growing body of evidence has demonstrated the regulatory impact of these innate-like T cells in central nervous system (CNS) diseases and that such immune cells can traffic into the brain in multiple pathological conditions, which can be typically attributed to the breakdown of the blood-brain barrier. However, until now, it has been poorly understood whether innate-like T cells have direct protective or causative properties, particularly in CNS diseases. Therefore, in this review, our attention is focused on discussing the critical roles of 3 unique subsets of unconventional T cells, namely, natural killer T cells, γδ T cells, and mucosal-associated invariant T cells, in the context of CNS diseases, disorders, and injuries and how the interplay of these immune cells modulates CNS pathology, in an attempt to gain a better understanding of their complex functions.

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  122. [130]130. Riva A, Patel V, Kurioka A, Jeffery HC, Wright G, Tarff S, et al. Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease. Gut. 2018;67(5):918-30. [PubMed: 29097439] Fig. 1. Type I and Type II NKT cells <!-- image --> NKT cells consist of Type I and Type II NKT cell populations. Type I (also known as iNKT cells) require the transcription factor PLZF for their development. Specific iNKT cell subpopulations use additional transcription factors for their effector functions (i.e., T-bet for NKT1; GATA-3 for NKT2; ROR γ t for NKT17). Type II NKT cells are highly variable in their T cell receptor (TCR) usage; as such, although some putative CD1d-presented antigens can be recognized by some Type II NKT cell subpopulations, the majority of this NKT cell subpopulation has highly diverse TCR usage and the antigens recognized by these cells are mostly unknown. Created with BioRender.com. Fig. 2. Brain-infiltrating γδ <!-- image --> T cells. γδ T cells can infiltrate and cross the disrupted BBB in the course of neurodegenerative diseases, leading to robust production of various cytokines including IL-17, IFNγ and TNFα that play a critical role in brain pathology. IL-17 secretion by γδ T cells is highly influenced by ROR γ t expression. Created with BioRender.com Identifying mucosal associated invariant T (MAIT) cell markers including CD3, CD4, CD8, Valpha 7.2 TCR, chemokine receptors: CCR5, CCR6, CCR9, and CXCR6, activation markers: CD25, CD69, CD44, CD38, and CD39, costimulatory/coinhibitory molecules: PD-1, CD28, and CD27. MAIT cells can release IL-10, IL-17, IL-22, Interferon (IFN) γ , TNF α , and granzyme B and the transcription factors, PLZF, ROR γ t, T-Bet, and Eomes. MAIT cells are activated through MR1 antigen presentation or through an antigen independent pathway through cytokines IL-18, IL-12, and IFN α . Created with BioRender.com. Fig. 3. MAIT cells <!-- image --> Table 1. The knowns and unknowns for innate-like T cells in CNS diseases and disorders

Cited by

Sorted by citations

Authors
Wyatt-Johnson, S. K., Afify, R., & Brutkiewicz, R. R.
Affiliations
Indiana University Indianapolis (US)
ORCID
Brutkiewicz, Randy R.
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2024-04
Volume
153
Issue
4
Pages
913-923
ISSN
0091-6749 (ISSN-L)
DOI
10.1016/j.jaci.2024.02.003
PMC
PMC10999338
OpenAlex
W4391848707
Cited by
17
References
5
Citations by year
2026: 7 · 2025: 9 · 2024: 1
FWCI
0.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Allergy and Clinical Immunology (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
  • National Institutes of Health
  • Alzheimer's Association
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
innate-like T cells, NKT cells, γδ T cells, mucosal-associated invariant T cells, central nervous system disorders, neuroinflammation, blood-brain barrier disruption, innate-adaptive immune interaction, neurological injury
MeSH terms
Mucosal-Associated Invariant T Cells, Central Nervous System Diseases, Humans, Immunity, Innate, Natural Killer T-Cells

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