Thermoneutral housing augments T cell receptor (TCR)-mediated CD4+ T cell responsiveness
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ABSTRACT: Mice (Mus musculus) used in biomedical research are commonly housed at 19-23 °C, below their thermoneutral zone (29-34 °C), where metabolic homeostasis occurs. Although traditional housing exposes mice to chronic cold stress and modulates their immune response, cellular mechanisms by which thermoneutrality shapes immune responses remain underdefined. CD4+ T cells are major contributors to host immunity through T cell receptor (TCR) signaling activated via recognition of peptide-major histocompatibility complex class II (pMHCII). We demonstrate that thermoneutral housing, compared to traditional conditions, enhances basal TCR signaling, upregulates genes associated with endogenous TCR stimulation, and increases TCR-driven TNF expression in CD4⁺ T cells. Mechanistically, these effects are in part dependent on basal TCR engagement with self-pMHCII. In inflammatory disease models, thermoneutrality-driven increased CD4⁺ T cell TNF production correlates with amplified tissue inflammation. Together, these findings reveal how housing temperature shapes inflammatory responses through self-pMHCII-dependent TCR signaling in CD4⁺ T cells.
ORGANISM(S): Mus musculus
PROVIDER: GSE310189 | GEO | 2026/03/31
REPOSITORIES: GEO
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