KEGG   PATHWAY: hsa04672
Entry
hsa04672                    Pathway                                
Name
Intestinal immune network for IgA production - Homo sapiens (human)
Description
The intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies that serve as the first line of defense against microorganisms. The basic map of IgA production includes induction of mucosal B cells in the Peyer's patches, circulation through the bloodstream and homing to intestinal mucosa of IgA-commited plasma cells, and local antibody production for export across the intestinal membranes. Multiple cytokines, including TGF-{beta}, IL-10, IL-4, IL-5, and IL-6, are required to promote IgA class switching and terminal differentiation process of the B cells. Secreted IgA promotes immune exclusion by entrapping dietary antigens and microorganisms in the mucus and functions for neutralization of toxins and pathogenic microbes.
Class
Organismal Systems; Immune system
Pathway map
hsa04672  Intestinal immune network for IgA production
hsa04672

Drug
D03203  Abatacept (USAN/INN)
D03222  Belatacept (USAN/INN)
D09799  Carotegrast methyl (JAN)
D09901  Etrolizumab (USAN/INN)
D10028  Valategrast hydrochloride (USAN)
D10378  Vercirnon (USAN/INN)
D10379  Vercirnon sodium (USAN)
D11281  Reltecimod (USAN/INN)
D11348  Reltecimod sodium (USAN)
D11556  Idecabtagene vicleucel (USAN)
D11594  Belantamab (USAN/INN)
D11595  Belantamab mafodotin (USAN)
D11821  Nogapendekin alfa (USAN/INN)
D11907  Rozibafusp alfa (USAN/INN)
D11992  Pavurutamab (USAN)
D11996  Feladilimab (USAN/INN)
D12010  Pacanalotamab (USAN)
D12151  Ianalumab (USAN/INN)
D12195  Izuralimab (USAN)
D12222  Linvoseltamab (USAN)
D12300  Acazicolcept (USAN/INN)
D12306  Ordesekimab (USAN)
D12315  Ciltacabtagene autoleucel (USAN/INN)
D12374  Sibeprenlimab (INN)
D12620  Frexalimab (USAN/INN)
D12623  Nanrilkefusp alfa (USAN/INN)
D12800  Zigakibart (USAN/INN)
D12803  Povetacicept (USAN/INN)
D12888  Nogapendekin alfa inbakicept
D12913  Ingitamig (USAN)
D12990  Etentamig (USAN/INN)
D13033  Abiprubart (USAN/INN)
Other DBs
GO: 0002387
Organism
Homo sapiens (human) [GN:hsa]
Gene
102723407  IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]
102723996  [KO:K06710]
10673  TNFSF13B; TNF superfamily member 13b [KO:K05476]
10803  CCR9; C-C motif chemokine receptor 9 [KO:K04184]
115650  TNFRSF13C; TNF receptor superfamily member 13C [KO:K05151]
23308  ICOSLG; inducible T cell costimulator ligand [KO:K06710]
23495  TNFRSF13B; TNF receptor superfamily member 13B [KO:K05150]
2826  CCR10; C-C motif chemokine receptor 10 [KO:K04185]
29851  ICOS; inducible T cell costimulator [KO:K06713]
3108  HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]
3109  HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]
3111  HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]
3112  HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]
3113  HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]
3115  HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]
3117  HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]
3118  HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
3119  HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]
3120  HLA-DQB2; major histocompatibility complex, class II, DQ beta 2 [KO:K06752]
3122  HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]
3123  HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]
3125  HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]
3126  HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]
3127  HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]
3558  IL2; interleukin 2 [KO:K05429]
3565  IL4; interleukin 4 [KO:K05430]
3567  IL5; interleukin 5 [KO:K05428]
3569  IL6; interleukin 6 [KO:K05405]
3586  IL10; interleukin 10 [KO:K05443]
3600  IL15; interleukin 15 [KO:K05433]
3601  IL15RA; interleukin 15 receptor subunit alpha [KO:K05074]
3676  ITGA4; integrin subunit alpha 4 [KO:K06483]
3695  ITGB7; integrin subunit beta 7 [KO:K06590]
4055  LTBR; lymphotoxin beta receptor [KO:K03159]
5284  PIGR; polymeric immunoglobulin receptor [KO:K13073]
56477  CCL28; C-C motif chemokine ligand 28 [KO:K05513]
57379  AICDA; activation induced cytidine deaminase [KO:K10989] [EC:3.5.4.38]
608  TNFRSF17; TNF receptor superfamily member 17 [KO:K05153]
6370  CCL25; C-C motif chemokine ligand 25 [KO:K13072]
6387  CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031]
7040  TGFB1; transforming growth factor beta 1 [KO:K13375]
7852  CXCR4; C-X-C motif chemokine receptor 4 [KO:K04189]
8174  MADCAM1; mucosal vascular addressin cell adhesion molecule 1 [KO:K06779]
8741  TNFSF13; TNF superfamily member 13 [KO:K05475]
9020  MAP3K14; mitogen-activated protein kinase kinase kinase 14 [KO:K04466] [EC:2.7.11.25]
940  CD28; CD28 molecule [KO:K06470]
941  CD80; CD80 molecule [KO:K05412]
942  CD86; CD86 molecule [KO:K05413]
958  CD40; CD40 molecule [KO:K03160]
959  CD40LG; CD40 ligand [KO:K03161]
Compound
C00777  Retinoate
C15493  9-cis-Retinoic acid
Reference
PMID:12511876
  Authors
Fagarasan S, Honjo T
  Title
Intestinal IgA synthesis: regulation of front-line body defences.
  Journal
Nat Rev Immunol 3:63-72 (2003)
DOI:10.1038/nri982
Reference
PMID:19079156
  Authors
Macpherson AJ, McCoy KD, Johansen FE, Brandtzaeg P
  Title
The immune geography of IgA induction and function.
  Journal
Mucosal Immunol 1:11-22 (2008)
DOI:10.1038/mi.2007.6
Reference
PMID:15971106
  Authors
Kunisawa J, Kiyono H
  Title
A marvel of mucosal T cells and secretory antibodies for the creation of first lines of defense.
  Journal
Cell Mol Life Sci 62:1308-21 (2005)
DOI:10.1007/s00018-005-5035-1
Reference
PMID:18549797
  Authors
Cerutti A, Rescigno M
  Title
The biology of intestinal immunoglobulin A responses.
  Journal
Immunity 28:740-50 (2008)
DOI:10.1016/j.immuni.2008.05.001
Reference
PMID:18243016
  Authors
Tsuji M, Suzuki K, Kinoshita K, Fagarasan S
  Title
Dynamic interactions between bacteria and immune cells leading to intestinal IgA synthesis.
  Journal
Semin Immunol 20:59-66 (2008)
DOI:10.1016/j.smim.2007.12.003
Reference
PMID:17182536
  Authors
Corthesy B
  Title
Roundtrip ticket for secretory IgA: role in mucosal homeostasis?
  Journal
J Immunol 178:27-32 (2007)
DOI:10.4049/jimmunol.178.1.27
Reference
PMID:18838301
  Authors
Suzuki K, Fagarasan S
  Title
How host-bacterial interactions lead to IgA synthesis in the gut.
  Journal
Trends Immunol 29:523-31 (2008)
DOI:10.1016/j.it.2008.08.001
Reference
PMID:19079167
  Authors
Mora JR, von Andrian UH
  Title
Differentiation and homing of IgA-secreting cells.
  Journal
Mucosal Immunol 1:96-109 (2008)
DOI:10.1038/mi.2007.14
Reference
PMID:17161619
  Authors
Suzuki K, Ha SA, Tsuji M, Fagarasan S
  Title
Intestinal IgA synthesis: a primitive form of adaptive immunity that regulates microbial communities in the gut.
  Journal
Semin Immunol 19:127-35 (2007)
DOI:10.1016/j.smim.2006.10.001
Reference
PMID:18483500
  Authors
Cerutti A
  Title
The regulation of IgA class switching.
  Journal
Nat Rev Immunol 8:421-34 (2008)
DOI:10.1038/nri2322
Related
pathway
hsa04612  Antigen processing and presentation
hsa04660  T cell receptor signaling pathway
hsa04662  B cell receptor signaling pathway
hsa04670  Leukocyte transendothelial migration
KO pathway
ko04672   

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