Innate Immune Response Disorder

[Guide]

The current, as of this date, most popular theory on rosacea was postulated by Dr. Richard Gallo at UCSD, who began postulating the 'innate immune system dysfunction' theory which is a complicated theory. It has become one of the most discussed and hopefully closer to the truth about what is at the heart of rosacea's cause, first postulated in an article in the June 1, 2004 Dermatolgy Times by Michelle Stephenson, who quotes Richard L. Gallo, M.D., Ph.D., saying rosacea may be an 'abnormality in the innate immune system...caused by too much cathelicidin." Dr Gallo says, "if we believe that the disease is caused by too much cathelicidin, we could develop a strategy to block the effects of the cathelicidins by making molecules that mimic that protein but don't have the same effects." Source. This may eventually happen; see Anti-Sting Therapy for Rosacea?

"Antimicrobial peptides are central effector molecules in skin immunology. The functions of antimicrobial peptides in skin diseases include the ability to act as cytokines or growth factors, driving disorders such as psoriasis and rosacea, as well as their action as natural antibiotics to control bacteria that influence diseases such as atopic dermatitis and acne."
Dermatol Clin. 2017 Jan;35(1):39-50
The Critical and Multifunctional Roles of Antimicrobial Peptides in Dermatology.
Takahashi T, Gallo RL

"Abnormalities of innate immunity can increase the skin’s susceptibility to the external environment, which might represent an influential factor in initiating or aggravating rosacea. Additionally, studies have also recently been conducted to identify possible abnormalities in adaptive immunity in rosacea, which might contribute to further inflammatory responses in rosacea."
Int J Mol Sci. 2016 Sep; 17(9): 1562.
Published online 2016 Sep 15. doi:  10.3390/ijms17091562, PMCID: PMC5037831
Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory Condition
Yu Ri Woo, Ji Hong Lim, Dae Ho Cho, and Hyun Jeong Park,

"Recent molecular studies suggest that an altered innate immune response is involved in the pathogenesis of the vascular and inflammatory disease seen in patients with rosacea."
Postgraduate Medicine, DOI: 10.3810/pgm.2009.09.2066
Updates on the Pathophysiology and Management of Acne Rosacea,
Mohamed L. Elsaie, MD, MBA and Sonal Choudhary, MD, 

"Rosacea is increasingly being viewed as an immune-based disorder."
Cutis. 2004 Jan;73(1 Suppl):5-8
Rosacea as an inflammatory disorder: a unifying theory?,
Millikan LE

"It is suggested that altered immune function plays a significant role in the pathogenesis of the disease."
Involvement of immune mechanisms in the pathogenesis of rosacea.
Br J Dermatol. 1982 Aug;107(2):203-8.
Manna V, Marks R, Holt P.

"Besides confirming the data in the literature on the positivity of the basal zone, anticollagen antibodies were found, and eluted antinuclear antibodies were detected against nuclei of cells in the epidermis and dermis, namely, scattered dermal, endothelial and eccrine duct cells."
Br J Dermatol. 1980 Nov;103(5):543-51.
Immunopathological studies on rosacea.
Nunzi E, Rebora A, Hamerlinck F, Cormane RH.

"Elevated ANA titers are commonly found in rosacea patients..."
Postep Derm Alergol 2013; XXX, 1: 1-5
Antinuclear antibodies in rosacea patients
Anna Woźniacka, Małgorzata Salamon, Daniel McCauliffe, Anna Sysa-Jędrzejowska

"Expression of TLR2, TLR4 and iNOS was higher in rosacea samples than in normal skin controls. This research demonstrates early and late stage components of innate immunity in specimens of rosacea ratifying the existence of an altered innate immunity in its pathogenesis."
Inate immunity in rosacea. Langerhans cells, plasmacytoid dentritic cells, Toll-like receptors and inducible oxide nitric synthase (iNOS) expression in skin specimens: case-control study.
Arch Dermatol Res. 2018 Jan 12;:
Moura AKA, Guedes F, Rivitti-Machado MC, Sotto MN

"TLR3-stimulated epidermal keratinocytes and rosacea epidermis enhance the expression of glucocorticoid-synthetic enzymes, which would promote cortisol activation in the epidermis. The innate immunity modulates glucocorticoid-synthetic enzymes expression via the TLR3 pathway in epidermal keratinocytes." 
J Dermatol Sci. 2020 Aug 29;:
TLR3 augments glucocorticoid-synthetic enzymes expression in epidermal keratinocytes; Implications of glucocorticoid metabolism in rosacea epidermis.
Shimada-Omori R, Yamasaki K, Koike S, Yamauchi T, Aiba S

"Individuals in our Down syndrome cohort had higher odds of a diagnosis with inflammatory and autoimmune presentations such as Alopecia areata (OR 6.06, p = 0.01), Other sepsis (OR 4.79, p < 0.001, Purpura and Other hemorrhagic conditions (OR 2.31, p < 0.001), and Rosacea (OR 3.11, p < 0.001)." 
Dysregulation of the Immune System in a Natural History Study of 1299 Individuals with Down Syndrome

More info on Cathlecidin

An interesting thread on this subject for your information.

Theories Revisited