The mucosal immune system protects the internal surfaces of the body, including those of the intestinal, respiratory and urogenital tracts. The mucosal surfaces are permeable barriers to the inner part of the body, which makes them especially vulnerable to the entry of pathogenic microorganisms and other antigens that can cause infections and inflammatory diseases. To prevent the entry of unwanted antigens, mucosal surfaces are lined by a mucus-secreting epithelium which represents our first line of defense.

To protect us while creating tolerance to symbiotic microbiota, the mucosal immune system has evolved very sophisticated mechanisms where specialized CD4+ T cells, CD8+ T cells (including intraepithelial lymphocytes-IELs), Innate Lymphoid cells (ILC), Ig-secreting plasma cells, macrophages and dendritic cells compromise between suppression and activation of an immune response. If this fine balance is disrupted, inflammatory conditions can arise. A clear example of this balance disruption is seen in inflammatory disorders in the gut in patients with inflammatory bowel disease or in the lung in allergic diseases.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract that includes Crohn’s disease and ulcerative colitis and is characterized by severe epithelium damage and intestinal inflammation. Although the pathogenesis of IBD is still unknown, several disease-associated genes, including NOD2 and ATG16L1 and IL23R, have been identified. The mucosal epithelium of IBD patients has decreased secretion of antimicrobial molecules, impaired bacterial recognition and defective IgA production leading to changes in microbiota composition and bacteria translocation. In response to microbial products, CD4+ T cells (Th1, Th2, Th17) are infiltrated to the lamina propria and secrete pro-inflammatory cytokines including TNF, IFN, IL-5, IL-6, IL-13, IL-17 or IL-22 5,16,17 through activation of certain STATs. In addition to T cells, innate lymphoid cells (ILC), NK cells and macrophages also secrete pro-inflammatory cytokines promoting epithelial damage, ulcers, and, in some cases, the development of colitis-associated cancer. Several of these cytokines are being investigated as potential targets for IBD treatment. In healthy individuals, regulatory T cells (Tregs) maintain immune tolerance and suppress effector T cell responses through anti-inflammatory cytokines such as IL‑10 and TGFβ. In contrast, Tregs are decreased in the gut of IBD patients.

Up to 30% of the population in industrialized countries suffers from allergy, and its prevalence is increasing over time. Allergic rhinitis and allergic asthma are the main allergic diseases affecting the upper and lower airways and are often seen co-existing in allergic patients. Allergy is characterized by the presence and production of immunoglobulin E (IgE), which binds to its main receptor (FcƐRI) in basophils and mast cells, and the subsequent release of histamine and leukotrienes. During the late phase, endothelial-cell adhesion and eosinophil recruitment increase, and T cells are activated. Activated Th1 and Th2 in the lungs secrete IL-5, IL-9 and IL-13, leading to allergic inflammation.

NOD2

Alternative names CARD-15, IBD1

Nucleotide oligomerization domain (NOD2), also known as CARD-15 or IBD1, is an intracellular pattern-recognition receptor involved in gastrointestinal immunity and expressed in monocytes and macrophages. Mutations in the NOD2 gene are associated with Crohn’s disease.

We recommend

NOD2 antibodies

NOD2 biochemicals

References

View 1 reference for NOD2

ATG16L1

Initiates the early phase of T-cell activation. May function as an important mediator of indirect neuronal damage in infectious and immune-mediated CNS diseases.

We recommend

Anti-CD4 antibody [EPR7276] (ab133622)

IL23R

T cell signaling; cytotoxic T cell-antigen interactions.

We recommend

CD8 antibodies

Defensins

Alternative names Interleukin-2 receptor subunit alpha, IL2RA, TAC antigen, TCGFR

Receptor for IL2 in complex with CD122 and CD132.

We recommend

Anti-IL-2 Receptor alpha antibody [EPR22816-65] (ab264557)

REG3

Alternative names TP44

Costimulation of T-cells. Induces T-cell activation and survival, interleukin-2 production, T-helper type 2 cell development and clonal expansion.

We recommend

Anti-CD28 antibody [EPR24592-5] (ab283860)

Cathelicidins

Toll-like receptors

TNF

TGF-beta

IL-10

Inflammasomes

Chemokines

TSLP

IL25

Il33

Il-4 and Il-13

IL-5

IL-9

References

NOD2

Hugot, JP.,, Chamaillard, M.,, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease Nature 411 ,509-603 (2001)

ATG16L1

Salem, M.,, Ammitzboell, M.,, Nys, K.,, et al. ATG16L1: A multifunctional susceptibility factor in Crohn disease Autophagy 11 (4),585-594 (2015)

IL23R

Naser, SA., Arce, M., Khaja, A., et al. Role of ATG16L, NOD2 and IL23R in Crohn's disease pathogenesis. World Journal of Gastroenterology 5 (18),412-424 (2012)

Defensins

Ramasundara, M., Leach, S. T., Lemberg, D.A., et al. Defensins and inflammation: the role of defensins in inflammatory bowel disease J Gastroenterol Hepatol 2 (24),202-208 (2009)

REG3

Shin, J. H., Seeley, R. J. REg3 proteins as gut hormones? Endocrinology 6 (160),1506-1514 (2019)

Edwards, J. A., Tan, N., Toussaint, N., et al. Role of regenerating islet-derived proteins in inflammatory bowel disease World J Gastroenterol 21 (26),2702-2714 (2020)

Cathelicidins

Sun, L., Wensheng, W. W., Xiao, W., Yang, H. The Roles of Cathelicidin LL-37 in Inflammatory Bowel Disease Inflammatory bowel diseases 8 (22),1986-1991 (2016)

Toll-like receptors

El-Zayat, S. R., Sibaii, H., Mannaa, F. A. Toll-like receptors activation, signaling, and targeting: an overview Bull Natl Res Cent 187 (43),187 (2019)

Lu, Y., Li, X., Liu, S. Toll-like Receptors and Inflammatory Bowel Disease Front Immunol 9 (72), (2018)

TNF

Neurath, M. F. Cytokines in inflammatory bowel disease Nature Rev Immunol 5 (14),329-342 (2014)

IL-10

Neurath, M. F. Cytokines in inflammatory bowel disease Nature Rev Immunol 5 (14),329-342 (2014)

Chemokines

Trivedi, P. J., Adams, D. H. Chemokines and Chemokine Receptors as Therapeutic Targets in Inflammatory Bowel Disease; Pitfalls and Promise J Crohns Colitis (12),641-652 (2018)

Danese, S., Gasbarrini, A. Chemokines in inflammatory bowel disease J Clin Pathol 10 (58),1025-1027 (2005)

Inflammasomes

Kelley, N., Jeltema, D., Duan, Y., et al. The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation Int J Mol Sci 13 (20),3328 (2019)

TSLP

Ziegler, S. F. Thymic stromal lymphopoietin and allergic disease J Allergy Clin Immunol 4 (130),845-852 (2012)

IL25

Yao, X., Sun, Y., Wang, W. Interleukin (IL)-25: Pleiotropic roles in asthma Respirology 4 (21),638-647 (2015)

IL-5

Pelaia, C., Paoletti, G., Puggioni, F., et al. Interleukin-5 in the Pathophysiology of Severe Asthma Front Physiol 10 ,1514 (2019)

IL-9

Bintha, A. U. K., Amadou, A. S., Huzzatul, M. M., Fauziyya, M. Therapeutic Potential of IL-9 in Allergic and Autoimmune Diseases IntechOpen , (2021)