Pathway Human Homo sapiens

Interleukin-10 signaling

R-HSA-6783783 in Reactome release 97: under Signaling by Interleukins, with 47 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-6783783 (mouse), R-RNO-6783783 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-6783783.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2016-12-12
Last updated: 2018-06-13
Events inside: 15, counted from the record

Interleukin-10 (IL10) was originally described as a factor named cytokine synthesis inhibitory factor that inhibited T-helper (Th) 1 activation and Th1 cytokine production (Fiorentino et al. 1989). It was found to be expressed by a variety of cell types including macrophages, dendritic cell subsets, B cells, several T-cell subpopulations including Th2 and T-regulatory cells (Tregs) and Natural Killer (NK) cells (Moore et al. 2001). It is now recognized that the biological effects of IL10 are directed at antigen-presenting cells (APCs) such as macrophages and dendritic cells (DCs), its effects on T-cell development and differentiation are largely indirect via inhibition of macrophage/dendritic cell activation and maturation (Pestka et al. 2004, Mocellin et al. 2004). T cells are thought to be the main source of IL10 (Hedrich & Bream 2010). IL10 inhibits a broad spectrum of activated macrophage/monocyte functions including monokine synthesis, NO production, and expression of class II MHC and costimulatory molecules such as IL12 and CD80/CD86 (de Waal Malefyt et al. 1991, Gazzinelli et al. 1992). Studies with recombinant cytokine and neutralizing antibodies revealed pleiotropic activities of IL10 on B, T, and mast cells (de Waal Malefyt et al. 1993, Rousset et al. 1992, Thompson-Snipes et al. 1991) and provided evidence for the in vivo significance of IL10 activities (Ishida et al. 1992, 1993). IL10 antagonizes the expression of MHC class II and the co-stimulatory molecules CD80/CD86 as well as the pro-inflammatory cytokines IL1Beta, IL6, IL8, TNFalpha and especially IL12 (Fiorentino et al. 1991, D'Andrea et al. 1993). The biological role of IL10 is not limited to inactivation of APCs, it also enhances B cell, granulocyte, mast cell, and keratinocyte growth/differentiation, as well as NK-cell and CD8+ cytotoxic T-cell activation (Moore et al. 2001, Hedrich & Bream 2010). IL10 also enhances NK-cell proliferation and/or production of IFN-gamma (Cai et al. 1999).

IL10-deficient mice exhibited inflammatory bowel disease (IBD) and other exaggerated inflammatory responses (Kuhn et al. 1993, Berg et al. 1995) indicating a critical role for IL10 in limiting inflammatory responses. Dysregulation of IL10 is linked with susceptibility to numerous infectious and autoimmune diseases in humans and mouse models (Hedrich & Bream 2010).

IL10 signaling is initiated by binding of homodimeric IL10 to the extracellular domains of two adjoining IL10RA molecules. This tetramer then binds two IL10RB chains. IL10RB cannot bind to IL10 unless bound to IL10RA (Ding et al. 2001, Yoon et al. 2006); binding of IL10 to IL10RA without the co-presence of IL10RB fails to initiate signal transduction (Kotenko et al. 1997).

IL10 binding activates the receptor-associated Janus tyrosine kinases, JAK1 and TYK2, which are constitutively bound to IL10R1 and IL10R2 respectively. In the classic model of receptor activation assembly of the receptor complex is believed to enable JAK1/TYK2 to phosphorylate and activate each other. Alternatively the binding of IL10 may cause conformational changes that allow the pseudokinase inhibitory domain of one JAK kinase to move away from the kinase domain of the other JAK within the receptor dimer-JAK complex, allowing the two kinase domains to interact and trans-activate (Waters & Brooks 2015).

The activated JAK kinases phosphorylate the intracellular domains of the IL10R1 chains on specific tyrosine residues. These phosphorylated tyrosine residues and their flanking peptide sequences serve as temporary docking sites for the latent, cytosolic, transcription factor, STAT3. STAT3 transiently docks on the IL10R1 chain via its SH2 domain, and is in turn tyrosine phosphorylated by the receptor-associated JAKs. Once activated, it dissociates from the receptor, dimerizes with other STAT3 molecules, and translocates to the nucleus where it binds with high affinity to STAT-binding elements (SBEs) in the promoters of IL-10-inducible genes (Donnelly et al. 1999).

Literature Reactome attaches

Interleukin-10 and the interleukin-10 receptorAnnu. Rev. Immunol., 2001, vol. 19, p. 683-765PubMed 11244051

Reactome's record lists 11 orthologous events, R-RNO-6783783 (Rattus norvegicus), R-MMU-6783783 (Mus musculus) among the species this site serves, and 9 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"Interleukin-10 signaling". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-6783783 with StableID: R-HSA-6783783.5 (accessed 2026-09-30 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 47 genes in this human pathway; showing 1 to 47, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneCCL19	AuthorityHGNC:10617	Mapping file id6363 NCBI file	EvidenceTAS
GeneCCL2	AuthorityHGNC:10618	Mapping file id6347 NCBI file	EvidenceTAS
GeneCCL20	AuthorityHGNC:10619	Mapping file id6364 NCBI file	EvidenceTAS
GeneCCL22	AuthorityHGNC:10621	Mapping file id6367 NCBI file	EvidenceTAS
GeneCCL3	AuthorityHGNC:10627	Mapping file id6348 NCBI file	EvidenceTAS
GeneCCL3L1	AuthorityHGNC:10628	Mapping file id6349 NCBI file	EvidenceTAS
GeneCCL3L3	AuthorityHGNC:30554	Mapping file id414062 NCBI file	EvidenceTAS
GeneCCL4	AuthorityHGNC:10630	Mapping file id6351 NCBI file	EvidenceTAS
GeneCCL4L1	AuthorityHGNC:10631	Mapping file id388372 NCBI file	EvidenceTAS
GeneCCL5	AuthorityHGNC:10632	Mapping file id6352 NCBI file	EvidenceTAS
GeneCCR1	AuthorityHGNC:1602	Mapping file id1230 NCBI file	EvidenceTAS
GeneCCR2	AuthorityHGNC:1603	Mapping file id729230 NCBI file	EvidenceTAS
GeneCCR5	AuthorityHGNC:1606	Mapping file id1234 NCBI file	EvidenceTAS
GeneCD80	AuthorityHGNC:1700	Mapping file id941 NCBI file	EvidenceTAS
GeneCD86	AuthorityHGNC:1705	Mapping file id942 NCBI file	EvidenceTAS
GeneCSF1	AuthorityHGNC:2432	Mapping file id1435 NCBI file	EvidenceTAS
GeneCSF2	AuthorityHGNC:2434	Mapping file id1437 NCBI file	EvidenceTAS
GeneCSF3	AuthorityHGNC:2438	Mapping file id1440 NCBI file	EvidenceTAS
GeneCXCL1	AuthorityHGNC:4602	Mapping file id2919 NCBI file	EvidenceTAS
GeneCXCL10	AuthorityHGNC:10637	Mapping file id3627 NCBI file	EvidenceTAS
GeneCXCL2	AuthorityHGNC:4603	Mapping file id2920 NCBI file	EvidenceTAS
GeneCXCL8	AuthorityHGNC:6025	Mapping file id3576 NCBI file	EvidenceTAS
GeneFCER2	AuthorityHGNC:3612	Mapping file id2208 NCBI file	EvidenceTAS
GeneFPR1	AuthorityHGNC:3826	Mapping file id2357 NCBI file	EvidenceTAS
GeneICAM1	AuthorityHGNC:5344	Mapping file id3383 NCBI file	EvidenceTAS
GeneIL10	AuthorityHGNC:5962	Mapping file id3586 NCBI file	EvidenceTAS
GeneIL10RA	AuthorityHGNC:5964	Mapping file id3587 NCBI file	EvidenceTAS
GeneIL10RB	AuthorityHGNC:5965	Mapping file id3588 NCBI file	EvidenceTAS
GeneIL12A	AuthorityHGNC:5969	Mapping file id3592 NCBI file	EvidenceTAS
GeneIL12B	AuthorityHGNC:5970	Mapping file id3593 NCBI file	EvidenceTAS
GeneIL18	AuthorityHGNC:5986	Mapping file id3606 NCBI file	EvidenceTAS
GeneIL1A	AuthorityHGNC:5991	Mapping file id3552 NCBI file	EvidenceTAS
GeneIL1B	AuthorityHGNC:5992	Mapping file id3553 NCBI file	EvidenceTAS
GeneIL1R1	AuthorityHGNC:5993	Mapping file id3554 NCBI file	EvidenceTAS
GeneIL1R2	AuthorityHGNC:5994	Mapping file id7850 NCBI file	EvidenceTAS
GeneIL1RN	AuthorityHGNC:6000	Mapping file id3557 NCBI file	EvidenceTAS
GeneIL6	AuthorityHGNC:6018	Mapping file id3569 NCBI file	EvidenceTAS
GeneJAK1	AuthorityHGNC:6190	Mapping file id3716 NCBI file	EvidenceTAS
GeneLIF	AuthorityHGNC:6596	Mapping file id3976 NCBI file	EvidenceTAS
GenePTAFR	AuthorityHGNC:9582	Mapping file id5724 NCBI file	EvidenceTAS
GenePTGS2	AuthorityHGNC:9605	Mapping file id5743 NCBI file	EvidenceTAS
GeneSTAT3	AuthorityHGNC:11364	Mapping file id6774 NCBI file	EvidenceTAS
GeneTIMP1	AuthorityHGNC:11820	Mapping file id7076 NCBI file	EvidenceTAS
GeneTNF	AuthorityHGNC:11892	Mapping file id7124 NCBI file	EvidenceTAS
GeneTNFRSF1A	AuthorityHGNC:11916	Mapping file id7132 NCBI file	EvidenceTAS
GeneTNFRSF1B	AuthorityHGNC:11917	Mapping file id7133 NCBI file	EvidenceTAS
GeneTYK2	AuthorityHGNC:12440	Mapping file id7297 NCBI file	EvidenceTAS

Evidence codes on this page: TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Signaling by InterleukinsR-HSA-449147465 genes

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.