GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE310nnn/GSE310189/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310189GEOGSEfalseThermoneutral housing augments T cell receptor (TCR)-mediated CD4+ T cell responsivenessMice (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.2026/03/31GSE310189GSM9290780GSM9290781GSM9290770GSM9290779GSM9290768GSM9290769GSM9290782GSM9290771GSM9290772GSM9290773GSM9290774GSM9290775GSM9290776GSM9290777GSM929077830172310189Mus musculus