Target type: biologicalprocess
Any process that stops, prevents, or reduces the frequency, rate or extent of T cell differentiation in the thymus. [GOC:add, GOC:mah]
Negative regulation of T cell differentiation in the thymus is a complex process that ensures the development of a functional and self-tolerant T cell repertoire. This process involves several checkpoints and signaling pathways that tightly control the progression of thymocytes, the immature T cells, through different stages of differentiation.
One key aspect of negative regulation is the elimination of autoreactive T cells, which can potentially target self-antigens and cause autoimmune diseases. This is achieved through mechanisms like clonal deletion and anergy. Clonal deletion involves the programmed death of thymocytes that express receptors recognizing self-antigens, preventing their maturation into functional T cells. Anergy, on the other hand, renders autoreactive T cells unresponsive to their target antigens, rendering them functionally inert.
Another critical component of negative regulation is the control of T cell lineage commitment. Thymocytes undergo a series of differentiation steps, transitioning from double-negative (DN) stages, lacking both CD4 and CD8 coreceptors, to double-positive (DP) stages, expressing both coreceptors, and finally to single-positive (SP) stages, expressing either CD4 or CD8. This process is tightly regulated by specific transcription factors and signaling pathways, ensuring proper lineage commitment and preventing aberrant differentiation.
Negative regulation also plays a vital role in shaping the functional diversity of T cell populations. The thymus generates a vast array of T cells with distinct specificities and effector functions. This diversity is achieved through the interplay of various regulatory mechanisms, including the selection of T cells based on their TCR affinity for self-antigens and the induction of specific differentiation programs.
In conclusion, negative regulation of T cell differentiation in the thymus is a multifaceted process that involves a complex interplay of signaling pathways, transcription factors, and cell death mechanisms. It ensures the development of a functional and self-tolerant T cell repertoire, protecting the organism from autoimmune diseases and maintaining immune homeostasis.'
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Protein | Definition | Taxonomy |
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Sonic hedgehog protein | A sonic hedgehog protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15465] | Homo sapiens (human) |
Bone morphogenetic protein 4 | A bone morphogenetic protein 4 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P12644] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
jervine | jervine: teratogen from Veratrum grandiflorum; RN given refers to parent cpd(3beta,23beta)-isomer; structure | piperidines | |
cyclopamine | piperidines | glioma-associated oncogene inhibitor | |
cur 61414 | CUR 61414: inhibits the hedehog signaling pathway; structure in first source | ||
dorsomorphin | dorsomorphin : A pyrazolopyrimidine that is pyrazolo[1,5-a]pyrimidine which is substituted at positions 3 and 6 by pyridin-4-yl and p-[2-(piperidin-1-yl)ethoxy]phenyl groups, respectively. It is a potent, selective, reversible, and ATP-competitive inhibitor of AMPK (AMP-activated protein kinase, EC 2.7.11.31) and a selective inhibitor of bone morphogenetic protein (BMP) signaling. dorsomorphin: an AMPK inhibitor | aromatic ether; piperidines; pyrazolopyrimidine; pyridines | bone morphogenetic protein receptor antagonist; EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} inhibitor |
gdc 0449 | HhAntag691: inhibits the hedgehog pathway and ABC transporters; has antineoplastic activity | benzamides; monochlorobenzenes; pyridines; sulfone | antineoplastic agent; Hedgehog signaling pathway inhibitor; SMO receptor antagonist; teratogenic agent |
robotnikinin | robotnikinin: binds sonic hedgehog protein to block its signaling pathway; structure in first source | ||
ldn 193189 | LDN 193189: inhibits bone morphogenetic protein signaling | pyrimidines | |
ml347 | ML347: an ALK2 inhibitor; structure in first source |