| 000 | 02498 am a22003253u 4500 | ||
|---|---|---|---|
| 042 | _adc | ||
| 100 | 1 | 0 |
_aSzeto, Aydan C. H. _eauthor _91958 |
| 700 | 1 | 0 |
_aFerreira, Ana C. F. _eauthor _91959 |
| 700 | 1 | 0 |
_aMannion, Jonathan _eauthor _91960 |
| 700 | 1 | 0 |
_aClark, Paula A. _eauthor _91961 |
| 700 | 1 | 0 |
_aSivasubramaniam, Meera _eauthor _91962 |
| 700 | 1 | 0 |
_aHeycock, Morgan W. D. _eauthor _91963 |
| 700 | 1 | 0 |
_aCrisp, Alastair _eauthor _91964 |
| 700 | 1 | 0 |
_aJolin, Helen E. _eauthor _91965 |
| 700 | 1 | 0 |
_aKozik, Patrycja _eauthor _91966 |
| 700 | 1 | 0 |
_aKnolle, Martin D. _eauthor _91967 |
| 700 | 1 | 0 |
_aMcKenzie, Andrew N. J. _eauthor _91968 |
| 245 | 0 | 0 | _aAn αvβ3 integrin checkpoint is critical for efficient T(H)2 cytokine polarisation and potentiating antigen-specific immunity |
| 260 | _c2023-01. | ||
| 500 | _a/pmc/articles/PMC7614022/ | ||
| 500 | _a/pubmed/36550322 | ||
| 520 | _aNaïve CD4(+) T lymphocytes initially undergo antigen-specific activation to promote a broad-spectrum response before adopting bespoke cytokine expression profiles shaped by intercellular microenvironmental cues, resulting in pathogen-focussed modular cytokine responses. Interleukin (IL)-4-induced Gata3 upregulation is important for the T helper 2 (T(H)2) cell polarisation associated with anti-helminth immunity and misdirected allergic inflammation. Whether additional microenvironmental factors participate is unclear. Using whole mouse-genome CRISPR-Cas9 screens we discovered a previously unappreciated role for αvβ3 integrin in T(H)2 cell differentiation. Low-level αvβ3 expression by naïve CD4(+) T cells contributed to pan-T cell activation by promoting T-T cell clustering and IL-2/CD25/STAT5-signalling. Subsequently, IL-4/Gata3-induced selective upregulation of αvβ3 licenced intercellular αvβ3-Thy1 interactions among T(H)2 cells, enhanced mTOR signalling, supported differentiation and promoted IL-5/IL-13 production. In mice, αvβ3 was required for efficient allergen-driven antigen-specific lung T(H)2 cell responses. Thus, αvβ3-expressing T(H)2 cells form multicellular factories to propagate and amplify T(H)2 responses. | ||
| 540 | _a | ||
| 540 | _ahttps://creativecommons.org/licenses/by/4.0/This work is licensed under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license. | ||
| 546 | _aen | ||
| 690 | _aArticle | ||
| 655 | 7 |
_aText _2local |
|
| 786 | 0 | _nNat Immunol | |
| 856 | 4 | 1 |
_uhttp://dx.doi.org/10.1038/s41590-022-01378-w _zConnect to this object online. |
| 999 |
_c859 _d859 |
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